Neil Osterweil

CHICAGO – Cetuximab combined with radiotherapy was no better than conventional chemoradiotherapy for the treatment of locally advanced squamous cell carcinomas of the head and neck, based on data from a phase II/III study presented at the annual meeting of the American Society of Clinical Oncology.

"No differences in activity and efficacy were observed between the two treatments," said Dr. Maria Grazia Ghi, of Ospedale Civile Venezia in Venice, Italy. However, while the treatments did not significantly differ in severe toxicities, compliance was better with concomitant therapy than with chemoradiotherapy (CRT), with more patients completing treatment and fewer having unplanned treatment interruptions, she noted.

The phase II/III study compared concomitant CRT with cetuximab and radiotherapy (CET/RT) – with and without induction therapy – with docetaxel, cisplatin, and 5-fluorouracil (TPF) in treatment-naive patients with unresectable squamous cell carcinomas of the head and neck. In 2010, phase II results were reported indicating that TPF induction was feasible in this population and did not compromise subsequent CRT. In addition, TPF induction chemotherapy significantly increased the chance of complete response (P = .004). Preliminary in-field toxicity results were reported at the 2012 ASCO meeting.

At this year’s meeting, data were presented on overall survival with or without induction therapy, and on grade 3 or worse in-field toxicities with CRT vs. CET/RT.

A total of 420 patients with squamous cell cancers of the oral cavity, hypopharynx, or oropharynx with good performance status (Eastern Cooperative Oncology Group 0 or 1) were randomized in a 2 x 2 factorial design to receive either TPF induction every 3 weeks for three cycles, or no induction, with each group then further randomized to either two cycles of cisplatin and 5-fluorouracil (5-FU) delivered concomitantly with 70 Gy of radiation divided into 35 fractions, or 7 weeks of cetuximab and the same radiotherapy dose.

There were no significant differences in the primary endpoint, in-field toxicities, with grade 3 mucositis occurring in 35% of patients on CRT, compared with 34% on CET/RT. Grade 4 mucositis occurred in 3% and 2% of patients, respectively. Grade 3 or 4 skin toxicities were also similar between the groups, with grade 3 adverse events seen in 12% of patients on CRT, vs. 19% on CET/RT, and grade 4 events occurring in 1% and 0.6%, respectively.

However, treatment compliance was significantly better with CRT, with 91% of patients assigned to this therapy completing both cycles, compared with 81% of patients assigned to CET/RT (P = .005). In addition, 23% of patients on CRT required interruption of radiotherapy for more than 3 consecutive days, compared with 38% of patients on CET/RT (P less than .001).

Median progression-free survival rates were 20.9 months for CRT vs. 20.7 months for CET/RT, a difference that was not significant. At 2 years, 48% of patients on CRT and 43% on CET/RT were alive without progression.

Median overall survival durations were 39.5 vs. 38.2 months, and overall survival at 2 years’ follow-up was 65% and 59%, respectively; the differences were not statistically significant.

There was an evident trend toward better progression-free survival and overall survival on CRT for patients with oropharyngeal cancers, but these differences were not significant at most recent follow-up, Dr. Ghi said.

Response rates to therapy, regardless of induction status, did not differ significantly, with 34% on CRT and 38% on CET/RT having a complete response, 47% and 46% having partial responses, 5% and 6% having stable disease, and 14% and 11% experiencing disease progression.

Invited discussant Dr. Danny Rischin, professor of oncology at the Peter MacCallum Cancer Centre in Melbourne, noted that the study was limited by its inclusion of patients from the randomized phase II induction comparison who were not later randomized to cetuximab, thereby confounding results of the phase III portion of the study. He added that it is still unknown whether there is an interaction between induction chemotherapy and the type of subsequent concomitant treatment, since the phase II data on the induction phase have not yet been reported.

Additionally, it is uncertain whether cisplatin/5-FU with a lower dose of cisplatin as given in this study – 20 mg/m² on days 1-4 – is equivalent to three cycles of cisplatin when given with conventionally fractionated radiation, Dr. Rischin said.

"We really need to wait for the final study results, including outcomes with TPF, and HPV [human papillomavirus] analyses, particularly for understanding what was happening in oropharyngeal cancer patients, and we need to see interaction results before drawing any final conclusions," he added.

Dr. Ghi reported having no relevant disclosures. Dr. Rischin reported receiving research funding from Genentech and Serono.

CHICAGO – Cetuximab combined with radiotherapy was no better than conventional chemoradiotherapy for the treatment of locally advanced squamous cell carcinomas of the head and neck, based on data from a phase II/III study presented at the annual meeting of the American Society of Clinical Oncology.

"No differences in activity and efficacy were observed between the two treatments," said Dr. Maria Grazia Ghi, of Ospedale Civile Venezia in Venice, Italy. However, while the treatments did not significantly differ in severe toxicities, compliance was better with concomitant therapy than with chemoradiotherapy (CRT), with more patients completing treatment and fewer having unplanned treatment interruptions, she noted.

The phase II/III study compared concomitant CRT with cetuximab and radiotherapy (CET/RT) – with and without induction therapy – with docetaxel, cisplatin, and 5-fluorouracil (TPF) in treatment-naive patients with unresectable squamous cell carcinomas of the head and neck. In 2010, phase II results were reported indicating that TPF induction was feasible in this population and did not compromise subsequent CRT. In addition, TPF induction chemotherapy significantly increased the chance of complete response (P = .004). Preliminary in-field toxicity results were reported at the 2012 ASCO meeting.

At this year’s meeting, data were presented on overall survival with or without induction therapy, and on grade 3 or worse in-field toxicities with CRT vs. CET/RT.

A total of 420 patients with squamous cell cancers of the oral cavity, hypopharynx, or oropharynx with good performance status (Eastern Cooperative Oncology Group 0 or 1) were randomized in a 2 x 2 factorial design to receive either TPF induction every 3 weeks for three cycles, or no induction, with each group then further randomized to either two cycles of cisplatin and 5-fluorouracil (5-FU) delivered concomitantly with 70 Gy of radiation divided into 35 fractions, or 7 weeks of cetuximab and the same radiotherapy dose.

There were no significant differences in the primary endpoint, in-field toxicities, with grade 3 mucositis occurring in 35% of patients on CRT, compared with 34% on CET/RT. Grade 4 mucositis occurred in 3% and 2% of patients, respectively. Grade 3 or 4 skin toxicities were also similar between the groups, with grade 3 adverse events seen in 12% of patients on CRT, vs. 19% on CET/RT, and grade 4 events occurring in 1% and 0.6%, respectively.

However, treatment compliance was significantly better with CRT, with 91% of patients assigned to this therapy completing both cycles, compared with 81% of patients assigned to CET/RT (P = .005). In addition, 23% of patients on CRT required interruption of radiotherapy for more than 3 consecutive days, compared with 38% of patients on CET/RT (P less than .001).

Median progression-free survival rates were 20.9 months for CRT vs. 20.7 months for CET/RT, a difference that was not significant. At 2 years, 48% of patients on CRT and 43% on CET/RT were alive without progression.

Median overall survival durations were 39.5 vs. 38.2 months, and overall survival at 2 years’ follow-up was 65% and 59%, respectively; the differences were not statistically significant.

There was an evident trend toward better progression-free survival and overall survival on CRT for patients with oropharyngeal cancers, but these differences were not significant at most recent follow-up, Dr. Ghi said.

Response rates to therapy, regardless of induction status, did not differ significantly, with 34% on CRT and 38% on CET/RT having a complete response, 47% and 46% having partial responses, 5% and 6% having stable disease, and 14% and 11% experiencing disease progression.

Invited discussant Dr. Danny Rischin, professor of oncology at the Peter MacCallum Cancer Centre in Melbourne, noted that the study was limited by its inclusion of patients from the randomized phase II induction comparison who were not later randomized to cetuximab, thereby confounding results of the phase III portion of the study. He added that it is still unknown whether there is an interaction between induction chemotherapy and the type of subsequent concomitant treatment, since the phase II data on the induction phase have not yet been reported.

Additionally, it is uncertain whether cisplatin/5-FU with a lower dose of cisplatin as given in this study – 20 mg/m² on days 1-4 – is equivalent to three cycles of cisplatin when given with conventionally fractionated radiation, Dr. Rischin said.

"We really need to wait for the final study results, including outcomes with TPF, and HPV [human papillomavirus] analyses, particularly for understanding what was happening in oropharyngeal cancer patients, and we need to see interaction results before drawing any final conclusions," he added.

Dr. Ghi reported having no relevant disclosures. Dr. Rischin reported receiving research funding from Genentech and Serono.

CHICAGO – Cetuximab combined with radiotherapy was no better than conventional chemoradiotherapy for the treatment of locally advanced squamous cell carcinomas of the head and neck, based on data from a phase II/III study presented at the annual meeting of the American Society of Clinical Oncology.

"No differences in activity and efficacy were observed between the two treatments," said Dr. Maria Grazia Ghi, of Ospedale Civile Venezia in Venice, Italy. However, while the treatments did not significantly differ in severe toxicities, compliance was better with concomitant therapy than with chemoradiotherapy (CRT), with more patients completing treatment and fewer having unplanned treatment interruptions, she noted.

The phase II/III study compared concomitant CRT with cetuximab and radiotherapy (CET/RT) – with and without induction therapy – with docetaxel, cisplatin, and 5-fluorouracil (TPF) in treatment-naive patients with unresectable squamous cell carcinomas of the head and neck. In 2010, phase II results were reported indicating that TPF induction was feasible in this population and did not compromise subsequent CRT. In addition, TPF induction chemotherapy significantly increased the chance of complete response (P = .004). Preliminary in-field toxicity results were reported at the 2012 ASCO meeting.

At this year’s meeting, data were presented on overall survival with or without induction therapy, and on grade 3 or worse in-field toxicities with CRT vs. CET/RT.

A total of 420 patients with squamous cell cancers of the oral cavity, hypopharynx, or oropharynx with good performance status (Eastern Cooperative Oncology Group 0 or 1) were randomized in a 2 x 2 factorial design to receive either TPF induction every 3 weeks for three cycles, or no induction, with each group then further randomized to either two cycles of cisplatin and 5-fluorouracil (5-FU) delivered concomitantly with 70 Gy of radiation divided into 35 fractions, or 7 weeks of cetuximab and the same radiotherapy dose.

There were no significant differences in the primary endpoint, in-field toxicities, with grade 3 mucositis occurring in 35% of patients on CRT, compared with 34% on CET/RT. Grade 4 mucositis occurred in 3% and 2% of patients, respectively. Grade 3 or 4 skin toxicities were also similar between the groups, with grade 3 adverse events seen in 12% of patients on CRT, vs. 19% on CET/RT, and grade 4 events occurring in 1% and 0.6%, respectively.

However, treatment compliance was significantly better with CRT, with 91% of patients assigned to this therapy completing both cycles, compared with 81% of patients assigned to CET/RT (P = .005). In addition, 23% of patients on CRT required interruption of radiotherapy for more than 3 consecutive days, compared with 38% of patients on CET/RT (P less than .001).

Median progression-free survival rates were 20.9 months for CRT vs. 20.7 months for CET/RT, a difference that was not significant. At 2 years, 48% of patients on CRT and 43% on CET/RT were alive without progression.

Median overall survival durations were 39.5 vs. 38.2 months, and overall survival at 2 years’ follow-up was 65% and 59%, respectively; the differences were not statistically significant.

There was an evident trend toward better progression-free survival and overall survival on CRT for patients with oropharyngeal cancers, but these differences were not significant at most recent follow-up, Dr. Ghi said.

Response rates to therapy, regardless of induction status, did not differ significantly, with 34% on CRT and 38% on CET/RT having a complete response, 47% and 46% having partial responses, 5% and 6% having stable disease, and 14% and 11% experiencing disease progression.

Invited discussant Dr. Danny Rischin, professor of oncology at the Peter MacCallum Cancer Centre in Melbourne, noted that the study was limited by its inclusion of patients from the randomized phase II induction comparison who were not later randomized to cetuximab, thereby confounding results of the phase III portion of the study. He added that it is still unknown whether there is an interaction between induction chemotherapy and the type of subsequent concomitant treatment, since the phase II data on the induction phase have not yet been reported.

Additionally, it is uncertain whether cisplatin/5-FU with a lower dose of cisplatin as given in this study – 20 mg/m² on days 1-4 – is equivalent to three cycles of cisplatin when given with conventionally fractionated radiation, Dr. Rischin said.

"We really need to wait for the final study results, including outcomes with TPF, and HPV [human papillomavirus] analyses, particularly for understanding what was happening in oropharyngeal cancer patients, and we need to see interaction results before drawing any final conclusions," he added.

Dr. Ghi reported having no relevant disclosures. Dr. Rischin reported receiving research funding from Genentech and Serono.

CHICAGO – For patients undergoing allogeneic bone marrow transplantation, conditioning with busulfan and fludarabine followed by post-transplant graft-vs.-host disease prophylaxis with single-agent cyclophosphamide is safe and is associated with good event-free and overall survival, said investigators at the annual meeting of the American Society of Clinical Oncology.

In a study of 92 patients with high-risk leukemias or myeloid malignancies, 2-year overall survival was 67%, and the rate of grade 3 or 4 acute graft-vs.-host disease (GVHD) was 15%, comparable to that seen with busulfan-cyclophosphamide conditioning regimens, said Dr. Christopher G. Kanakry, a medical oncologist at the Sidney Kimmel Cancer Center at John Hopkins Medical Center in Baltimore.

Neil Osterweil/IMNG Medical Media

Chronic GVHD was seen in 14% of all patients, occurring in only 7% of patients with related donors, and 22% of those with unrelated donors (P = .041). Event-free survival at 2 years was 62% and did not differ by donor type, Dr. Kanakry said.

"Post-transplant single-agent GVHD prophylaxis can be safely and effectively combined with busulfan/fludarabine myeloablative conditioning and is associated with an acceptable incidence of grade 2-4 acute graft-vs.-host disease, a low incidence of grade 3-4 acute graft-vs.-host disease and chronic graft-vs.-host disease, low treatment-related mortality, and effective disease control with favorable event-free and overall survival," he said.

Dr. Kanakry and his colleagues at Johns Hopkins, the Fred Hutchinson Cancer Center in Seattle and the University of Texas MD Anderson Cancer Center in Houston combined efforts to see whether the clinical efficacy seen in single-center studies with busulfan/fludarabine conditioning and cyclophosphamide GVHD prophylaxis could be safely combined.

They enrolled patients with high-risk hematologic malignancies, including patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia in first complete remission with high-risk features, acute leukemias in second or greater remission, refractory or relapsed AML with 10% or fewer bone marrow blasts, myelodysplastic syndrome with high-risk features, chronic myeloid leukemia beyond the first chronic phase or resistant to tyrosine kinase inhibitors, Philadelphia chromosome–negative myeloproliferative disorders, relapsed chemotherapy-sensitive Hodgkin or non-Hodgkin lymphoma, or stage III multiple myeloma.

Of the 92 patients enrolled, 45 had related donors and 47 had unrelated donors.

Grade 2-4 acute GVHD occurred in 51% of patients, 42% of those with related donors, and 60% with unrelated donors (P = .027). Chronic GVHD occurred in six patients (14%), three of whom had bronchiolitis obliterans syndrome. The incidence of chronic GVHD also was significantly higher among patients with unrelated donors (P = .041).

Among all patients, 9% died from nonrelapse causes within the first 100 days of transplant, and 16% died within 1 year. There was no difference in the incidence of nonrelapse mortality between related and unrelated donors.

Not surprisingly, patients with complete remissions had significantly better 2-year event-free survival, at 80%, compared with 50% for patients with minimal residual disease, and 33% for patients with active disease (P = .0005).

Overall 2-year survival for all patients was 67% and did not differ by donor type. Overall survival was significantly better for patients with complete remissions, 79% of whom were alive at 2 years, compared with 50% of those with minimal residual disease, and 54% of those with active disease (P = .019).

Invited discussant Dr. Marcos J.G. De Lima, a hematologist-oncologist at University Hospitals Case Western Medical Center in Cleveland noted that the regimen is relatively simple, comparatively inexpensive, and reproducible.

"Could a cynic say that less chronic GVHD was due to the fact that you were using bone marrow only? I don’t think so, but certainly there is a bone marrow component [to the GVHD results]," he said.

The investigators also did not determine whether patients had ever taken other immunosuppressants, such as calcineurin inhibitors, Dr. De Lima said,

"I want to remind you folks that one of the most frustrating things in our business is that even when we reduce the incidence of acute GVHD, very few strategies have translated into less chronic [GVHD]; it’s like there is a different life between acute and chronic GVHD, and here it’s almost the opposite, which is very intriguing," he said.

The study was supported by Otsuka Pharmaceuticals. Dr. Kanakry reported having no relevant disclosures. Dr. De Lima was a coauthor of the study. He disclosed receiving research funding from Celgene.

CHICAGO – For patients undergoing allogeneic bone marrow transplantation, conditioning with busulfan and fludarabine followed by post-transplant graft-vs.-host disease prophylaxis with single-agent cyclophosphamide is safe and is associated with good event-free and overall survival, said investigators at the annual meeting of the American Society of Clinical Oncology.

In a study of 92 patients with high-risk leukemias or myeloid malignancies, 2-year overall survival was 67%, and the rate of grade 3 or 4 acute graft-vs.-host disease (GVHD) was 15%, comparable to that seen with busulfan-cyclophosphamide conditioning regimens, said Dr. Christopher G. Kanakry, a medical oncologist at the Sidney Kimmel Cancer Center at John Hopkins Medical Center in Baltimore.

Neil Osterweil/IMNG Medical Media

Chronic GVHD was seen in 14% of all patients, occurring in only 7% of patients with related donors, and 22% of those with unrelated donors (P = .041). Event-free survival at 2 years was 62% and did not differ by donor type, Dr. Kanakry said.

"Post-transplant single-agent GVHD prophylaxis can be safely and effectively combined with busulfan/fludarabine myeloablative conditioning and is associated with an acceptable incidence of grade 2-4 acute graft-vs.-host disease, a low incidence of grade 3-4 acute graft-vs.-host disease and chronic graft-vs.-host disease, low treatment-related mortality, and effective disease control with favorable event-free and overall survival," he said.

Dr. Kanakry and his colleagues at Johns Hopkins, the Fred Hutchinson Cancer Center in Seattle and the University of Texas MD Anderson Cancer Center in Houston combined efforts to see whether the clinical efficacy seen in single-center studies with busulfan/fludarabine conditioning and cyclophosphamide GVHD prophylaxis could be safely combined.

They enrolled patients with high-risk hematologic malignancies, including patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia in first complete remission with high-risk features, acute leukemias in second or greater remission, refractory or relapsed AML with 10% or fewer bone marrow blasts, myelodysplastic syndrome with high-risk features, chronic myeloid leukemia beyond the first chronic phase or resistant to tyrosine kinase inhibitors, Philadelphia chromosome–negative myeloproliferative disorders, relapsed chemotherapy-sensitive Hodgkin or non-Hodgkin lymphoma, or stage III multiple myeloma.

Of the 92 patients enrolled, 45 had related donors and 47 had unrelated donors.

Grade 2-4 acute GVHD occurred in 51% of patients, 42% of those with related donors, and 60% with unrelated donors (P = .027). Chronic GVHD occurred in six patients (14%), three of whom had bronchiolitis obliterans syndrome. The incidence of chronic GVHD also was significantly higher among patients with unrelated donors (P = .041).

Among all patients, 9% died from nonrelapse causes within the first 100 days of transplant, and 16% died within 1 year. There was no difference in the incidence of nonrelapse mortality between related and unrelated donors.

Not surprisingly, patients with complete remissions had significantly better 2-year event-free survival, at 80%, compared with 50% for patients with minimal residual disease, and 33% for patients with active disease (P = .0005).

Overall 2-year survival for all patients was 67% and did not differ by donor type. Overall survival was significantly better for patients with complete remissions, 79% of whom were alive at 2 years, compared with 50% of those with minimal residual disease, and 54% of those with active disease (P = .019).

Invited discussant Dr. Marcos J.G. De Lima, a hematologist-oncologist at University Hospitals Case Western Medical Center in Cleveland noted that the regimen is relatively simple, comparatively inexpensive, and reproducible.

"Could a cynic say that less chronic GVHD was due to the fact that you were using bone marrow only? I don’t think so, but certainly there is a bone marrow component [to the GVHD results]," he said.

The investigators also did not determine whether patients had ever taken other immunosuppressants, such as calcineurin inhibitors, Dr. De Lima said,

"I want to remind you folks that one of the most frustrating things in our business is that even when we reduce the incidence of acute GVHD, very few strategies have translated into less chronic [GVHD]; it’s like there is a different life between acute and chronic GVHD, and here it’s almost the opposite, which is very intriguing," he said.

The study was supported by Otsuka Pharmaceuticals. Dr. Kanakry reported having no relevant disclosures. Dr. De Lima was a coauthor of the study. He disclosed receiving research funding from Celgene.

CHICAGO – For patients undergoing allogeneic bone marrow transplantation, conditioning with busulfan and fludarabine followed by post-transplant graft-vs.-host disease prophylaxis with single-agent cyclophosphamide is safe and is associated with good event-free and overall survival, said investigators at the annual meeting of the American Society of Clinical Oncology.

In a study of 92 patients with high-risk leukemias or myeloid malignancies, 2-year overall survival was 67%, and the rate of grade 3 or 4 acute graft-vs.-host disease (GVHD) was 15%, comparable to that seen with busulfan-cyclophosphamide conditioning regimens, said Dr. Christopher G. Kanakry, a medical oncologist at the Sidney Kimmel Cancer Center at John Hopkins Medical Center in Baltimore.

Neil Osterweil/IMNG Medical Media

Chronic GVHD was seen in 14% of all patients, occurring in only 7% of patients with related donors, and 22% of those with unrelated donors (P = .041). Event-free survival at 2 years was 62% and did not differ by donor type, Dr. Kanakry said.

"Post-transplant single-agent GVHD prophylaxis can be safely and effectively combined with busulfan/fludarabine myeloablative conditioning and is associated with an acceptable incidence of grade 2-4 acute graft-vs.-host disease, a low incidence of grade 3-4 acute graft-vs.-host disease and chronic graft-vs.-host disease, low treatment-related mortality, and effective disease control with favorable event-free and overall survival," he said.

Dr. Kanakry and his colleagues at Johns Hopkins, the Fred Hutchinson Cancer Center in Seattle and the University of Texas MD Anderson Cancer Center in Houston combined efforts to see whether the clinical efficacy seen in single-center studies with busulfan/fludarabine conditioning and cyclophosphamide GVHD prophylaxis could be safely combined.

They enrolled patients with high-risk hematologic malignancies, including patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia in first complete remission with high-risk features, acute leukemias in second or greater remission, refractory or relapsed AML with 10% or fewer bone marrow blasts, myelodysplastic syndrome with high-risk features, chronic myeloid leukemia beyond the first chronic phase or resistant to tyrosine kinase inhibitors, Philadelphia chromosome–negative myeloproliferative disorders, relapsed chemotherapy-sensitive Hodgkin or non-Hodgkin lymphoma, or stage III multiple myeloma.

Of the 92 patients enrolled, 45 had related donors and 47 had unrelated donors.

Grade 2-4 acute GVHD occurred in 51% of patients, 42% of those with related donors, and 60% with unrelated donors (P = .027). Chronic GVHD occurred in six patients (14%), three of whom had bronchiolitis obliterans syndrome. The incidence of chronic GVHD also was significantly higher among patients with unrelated donors (P = .041).

Among all patients, 9% died from nonrelapse causes within the first 100 days of transplant, and 16% died within 1 year. There was no difference in the incidence of nonrelapse mortality between related and unrelated donors.

Not surprisingly, patients with complete remissions had significantly better 2-year event-free survival, at 80%, compared with 50% for patients with minimal residual disease, and 33% for patients with active disease (P = .0005).

Overall 2-year survival for all patients was 67% and did not differ by donor type. Overall survival was significantly better for patients with complete remissions, 79% of whom were alive at 2 years, compared with 50% of those with minimal residual disease, and 54% of those with active disease (P = .019).

Invited discussant Dr. Marcos J.G. De Lima, a hematologist-oncologist at University Hospitals Case Western Medical Center in Cleveland noted that the regimen is relatively simple, comparatively inexpensive, and reproducible.

"Could a cynic say that less chronic GVHD was due to the fact that you were using bone marrow only? I don’t think so, but certainly there is a bone marrow component [to the GVHD results]," he said.

The investigators also did not determine whether patients had ever taken other immunosuppressants, such as calcineurin inhibitors, Dr. De Lima said,

"I want to remind you folks that one of the most frustrating things in our business is that even when we reduce the incidence of acute GVHD, very few strategies have translated into less chronic [GVHD]; it’s like there is a different life between acute and chronic GVHD, and here it’s almost the opposite, which is very intriguing," he said.

The study was supported by Otsuka Pharmaceuticals. Dr. Kanakry reported having no relevant disclosures. Dr. De Lima was a coauthor of the study. He disclosed receiving research funding from Celgene.

CHICAGO – Retreating unresectable gastrointestinal stromal tumors with imatinib after disease progression can improve both progression-free survival and disease control rates, but the benefits of rechallenge are short lived, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Imatinib rechallenge is commonly tried in patients with gastrointestinal stromal tumors (GIST) that have progressed after an initial response to imatinib (Gleevec) in the first line and sunitinib (Sutent) or another tyrosine kinase inhibitor (TKI) in the second line, but without empirical evidence to support the practice, said Dr. Yoon-Koo Kang, professor of oncology at Seoul National University in Seoul, South Korea.

In the phase III RIGHT (Rechallenge of imatinib in GIST having no effective treatment) trial, patients who were randomized to imatinib rechallenge had a small but significant benefit in progression-free survival (PFS), with a median of 1.8 months compared with 0.9 months for patients assigned to placebo (hazard ratio [HR] 0.45, P = .00075).

In addition, significantly more patients retreated with imatinib had stable disease lasting at least 4 weeks (30 vs. 17 patients, P = .005), 8 weeks (17 vs.6, P = .008), or 12 weeks (13 vs. 2, P = .003).

"Rechallenge of imatinib significantly improves progression-free survival and disease-control rate in patients with advanced GIST after failure of at least imatinib and sunitinib, likely by continuous kinase inhibition of the bulk of disease clones which retain imatinib sensitivity. However, TKI-resistant clones continue to progress, leading to relatively brief duration of benefit," said Dr. Kang.

The investigators enrolled patients with metastatic and/or unresectable GIST who had previously had either disease control with first-line imatinib for longer than 6 months, or who experienced disease progression on both first-line imatinib and second-line sunitinib. The patients had Eastern Cooperative Oncology Group (ECOG) performance status scores from 0 to 3.

A total of 41 patients were randomized in a double-blinded fashion to imatinib until disease progression, at which point they could stop or continue on imatinib, and 40 were randomized to placebo until disease progression, after which they could be crossed over to receive imatinib. In each group, 16 patients had previously received treatment with three or more TKIs, including nilotinib (Tasigna), sorafenib (Nexavar), regorafenib (Stivarga), or dovitinib.

Of the 40 patients in the placebo arm, 37 crossed over to imatinib after disease progression. Median PFS after crossover in these patients approached that of patients initially assigned to imatinib at 1.7 months.

Grade 3 or 4 fatigue occurred in four patients on imatinib vs. none on placebo, and grade 3 or 4 hyperbilirubinemia occurred in three patients and one patient, respectively. Grade 3 or 4 anemias were detected in 12 patients on imatinib vs. 3 on placebo.

The trial demonstrates the wisdom of the adage "if at first you don’t succeed, try, try again," said invited discussant Dr. Shreyaskumar Patel, professor of sarcoma oncology at the University of Texas MD Anderson Cancer Center in Houston.

If patients have "run out of all sorts of options, randomizing them to imatinib instead of placebo certainly slows down the rate of progression, even in the absence of a response, and certainly can [have an] impact on their overall quality of life and their natural history," he said.

The results also support the use of a kinase inhibitor rather than placebo in the control arm of future trials for novel anti-GIST agents, he added.

Dr. Kang and Dr. Patel disclosed ties to Novartis. Dr. Kang disclosed ties with Novartis and Bayer Schering Pharma. The RIGHT trial was sponsored in part by Novartis.

CHICAGO – Retreating unresectable gastrointestinal stromal tumors with imatinib after disease progression can improve both progression-free survival and disease control rates, but the benefits of rechallenge are short lived, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Imatinib rechallenge is commonly tried in patients with gastrointestinal stromal tumors (GIST) that have progressed after an initial response to imatinib (Gleevec) in the first line and sunitinib (Sutent) or another tyrosine kinase inhibitor (TKI) in the second line, but without empirical evidence to support the practice, said Dr. Yoon-Koo Kang, professor of oncology at Seoul National University in Seoul, South Korea.

In the phase III RIGHT (Rechallenge of imatinib in GIST having no effective treatment) trial, patients who were randomized to imatinib rechallenge had a small but significant benefit in progression-free survival (PFS), with a median of 1.8 months compared with 0.9 months for patients assigned to placebo (hazard ratio [HR] 0.45, P = .00075).

In addition, significantly more patients retreated with imatinib had stable disease lasting at least 4 weeks (30 vs. 17 patients, P = .005), 8 weeks (17 vs.6, P = .008), or 12 weeks (13 vs. 2, P = .003).

"Rechallenge of imatinib significantly improves progression-free survival and disease-control rate in patients with advanced GIST after failure of at least imatinib and sunitinib, likely by continuous kinase inhibition of the bulk of disease clones which retain imatinib sensitivity. However, TKI-resistant clones continue to progress, leading to relatively brief duration of benefit," said Dr. Kang.

The investigators enrolled patients with metastatic and/or unresectable GIST who had previously had either disease control with first-line imatinib for longer than 6 months, or who experienced disease progression on both first-line imatinib and second-line sunitinib. The patients had Eastern Cooperative Oncology Group (ECOG) performance status scores from 0 to 3.

A total of 41 patients were randomized in a double-blinded fashion to imatinib until disease progression, at which point they could stop or continue on imatinib, and 40 were randomized to placebo until disease progression, after which they could be crossed over to receive imatinib. In each group, 16 patients had previously received treatment with three or more TKIs, including nilotinib (Tasigna), sorafenib (Nexavar), regorafenib (Stivarga), or dovitinib.

Of the 40 patients in the placebo arm, 37 crossed over to imatinib after disease progression. Median PFS after crossover in these patients approached that of patients initially assigned to imatinib at 1.7 months.

Grade 3 or 4 fatigue occurred in four patients on imatinib vs. none on placebo, and grade 3 or 4 hyperbilirubinemia occurred in three patients and one patient, respectively. Grade 3 or 4 anemias were detected in 12 patients on imatinib vs. 3 on placebo.

The trial demonstrates the wisdom of the adage "if at first you don’t succeed, try, try again," said invited discussant Dr. Shreyaskumar Patel, professor of sarcoma oncology at the University of Texas MD Anderson Cancer Center in Houston.

If patients have "run out of all sorts of options, randomizing them to imatinib instead of placebo certainly slows down the rate of progression, even in the absence of a response, and certainly can [have an] impact on their overall quality of life and their natural history," he said.

The results also support the use of a kinase inhibitor rather than placebo in the control arm of future trials for novel anti-GIST agents, he added.

Dr. Kang and Dr. Patel disclosed ties to Novartis. Dr. Kang disclosed ties with Novartis and Bayer Schering Pharma. The RIGHT trial was sponsored in part by Novartis.

CHICAGO – Retreating unresectable gastrointestinal stromal tumors with imatinib after disease progression can improve both progression-free survival and disease control rates, but the benefits of rechallenge are short lived, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Imatinib rechallenge is commonly tried in patients with gastrointestinal stromal tumors (GIST) that have progressed after an initial response to imatinib (Gleevec) in the first line and sunitinib (Sutent) or another tyrosine kinase inhibitor (TKI) in the second line, but without empirical evidence to support the practice, said Dr. Yoon-Koo Kang, professor of oncology at Seoul National University in Seoul, South Korea.

In the phase III RIGHT (Rechallenge of imatinib in GIST having no effective treatment) trial, patients who were randomized to imatinib rechallenge had a small but significant benefit in progression-free survival (PFS), with a median of 1.8 months compared with 0.9 months for patients assigned to placebo (hazard ratio [HR] 0.45, P = .00075).

In addition, significantly more patients retreated with imatinib had stable disease lasting at least 4 weeks (30 vs. 17 patients, P = .005), 8 weeks (17 vs.6, P = .008), or 12 weeks (13 vs. 2, P = .003).

"Rechallenge of imatinib significantly improves progression-free survival and disease-control rate in patients with advanced GIST after failure of at least imatinib and sunitinib, likely by continuous kinase inhibition of the bulk of disease clones which retain imatinib sensitivity. However, TKI-resistant clones continue to progress, leading to relatively brief duration of benefit," said Dr. Kang.

The investigators enrolled patients with metastatic and/or unresectable GIST who had previously had either disease control with first-line imatinib for longer than 6 months, or who experienced disease progression on both first-line imatinib and second-line sunitinib. The patients had Eastern Cooperative Oncology Group (ECOG) performance status scores from 0 to 3.

A total of 41 patients were randomized in a double-blinded fashion to imatinib until disease progression, at which point they could stop or continue on imatinib, and 40 were randomized to placebo until disease progression, after which they could be crossed over to receive imatinib. In each group, 16 patients had previously received treatment with three or more TKIs, including nilotinib (Tasigna), sorafenib (Nexavar), regorafenib (Stivarga), or dovitinib.

Of the 40 patients in the placebo arm, 37 crossed over to imatinib after disease progression. Median PFS after crossover in these patients approached that of patients initially assigned to imatinib at 1.7 months.

Grade 3 or 4 fatigue occurred in four patients on imatinib vs. none on placebo, and grade 3 or 4 hyperbilirubinemia occurred in three patients and one patient, respectively. Grade 3 or 4 anemias were detected in 12 patients on imatinib vs. 3 on placebo.

The trial demonstrates the wisdom of the adage "if at first you don’t succeed, try, try again," said invited discussant Dr. Shreyaskumar Patel, professor of sarcoma oncology at the University of Texas MD Anderson Cancer Center in Houston.

If patients have "run out of all sorts of options, randomizing them to imatinib instead of placebo certainly slows down the rate of progression, even in the absence of a response, and certainly can [have an] impact on their overall quality of life and their natural history," he said.

The results also support the use of a kinase inhibitor rather than placebo in the control arm of future trials for novel anti-GIST agents, he added.

Dr. Kang and Dr. Patel disclosed ties to Novartis. Dr. Kang disclosed ties with Novartis and Bayer Schering Pharma. The RIGHT trial was sponsored in part by Novartis.

CHICAGO – When paired with rituximab, the experimental agent idelalisib was associated with durable progression-free survival rates in older patients with treatment-naive chronic lymphocytic leukemia or small lymphocytic lymphoma, Dr. Susan M. O’Brien reported at the annual meeting of the American Society of Clinical Oncology.

Among 64 patients in an open-label phase II study, the overall response rate was 97%, consisting of 19% complete responses and 78% partial responses. Among 9 patients with chromosome 17 abnormalities, which are associated with a poor prognosis, 3 had a complete response and 6 had a partial response, said Dr. O’Brien, of the University of Texas MD Anderson Cancer Center in Houston.

Progression-free survival (PFS) at 24 months was 93% among all patients, and 100% among the 9 patients with the poor-prognosis TP53 mutation or a deletion in chromosome 17 (17p).

"I think that these data, particularly the PFS, really support further evaluation of this agent in front-line CLL [chronic lymphocytic leukemia]," she said.

Idelalisib (GS-1101) is a targeted, highly selective oral inhibitor of the P13 kinase delta isoform (P13K-delta). The oral drug inhibits proliferation of many B-cell malignancies and induces apoptosis, and it inhibits homing and retention of malignant B cells in lymphoid tissues, Dr. O’Brien explained.

In a phase I trial also reported at this year’s ASCO meeting, 72% of 54 patients with relapsed/refractory CLL treated with single agent idelalisib had a partial response, with a 1-month median time to response and a response duration of 16-plus months, reported Dr. Jennifer R. Brown, director of the Chronic Lymphocytic Leukemia Center at the Dana-Farber Cancer Institute in Boston.

In the phase II study conducted by Dr. O’Brien, patients aged 65 years and older with previously untreated CLL were given idelalisib 150 mg twice daily for 48 weeks and rituximab 375 mg/m² once weekly for 8 weeks. Disease status was determined by investigators. Those patients who did not have disease progression after 48 weeks were allowed to stay on therapy in an extension study.

In the primary study, 62 of 64 patients completed the 8 weeks of therapy with rituximab and idelalisib, and 43 completed all 48 weeks. Of the 21 who discontinued therapy, 17 did so because of adverse events, 3 died, and 1 withdrew consent. Of 40 patients enrolled in the extension phase of the trial, 33 were still on study as of May 2013. Of the 7 patients who withdrew from the extension study, 6 did so because of adverse events and 1 withdrew consent.

Of the 64 patients started on the drug combination in the primary study, 12 had a complete response, and 3 of these patients had a 17p deletion and/or TP53 mutation. Partial responses occurred in 50 patients, 6 of whom had mutations or deletions.

In all, 23% of patients in the primary and extension studies had grade 3 diarrhea and/or colitis. Grade 3 or greater pneumonia occurred in 17%, transaminase elevations in 23%, and neutropenia in 28%. Of the patients who discontinued therapy due to adverse events, 5 did so because of respiratory events in the first 24 weeks, and 5 did so because of diarrhea/colitis during the extension study. Other causes of discontinuation were anemia and elevated transaminases.

The study was sponsored by Gilead Sciences. Dr. O’Brien disclosed receiving research funding from the company. Dr. Brown reported having no relevant financial disclosures.

CHICAGO – When paired with rituximab, the experimental agent idelalisib was associated with durable progression-free survival rates in older patients with treatment-naive chronic lymphocytic leukemia or small lymphocytic lymphoma, Dr. Susan M. O’Brien reported at the annual meeting of the American Society of Clinical Oncology.

Among 64 patients in an open-label phase II study, the overall response rate was 97%, consisting of 19% complete responses and 78% partial responses. Among 9 patients with chromosome 17 abnormalities, which are associated with a poor prognosis, 3 had a complete response and 6 had a partial response, said Dr. O’Brien, of the University of Texas MD Anderson Cancer Center in Houston.

Progression-free survival (PFS) at 24 months was 93% among all patients, and 100% among the 9 patients with the poor-prognosis TP53 mutation or a deletion in chromosome 17 (17p).

"I think that these data, particularly the PFS, really support further evaluation of this agent in front-line CLL [chronic lymphocytic leukemia]," she said.

Idelalisib (GS-1101) is a targeted, highly selective oral inhibitor of the P13 kinase delta isoform (P13K-delta). The oral drug inhibits proliferation of many B-cell malignancies and induces apoptosis, and it inhibits homing and retention of malignant B cells in lymphoid tissues, Dr. O’Brien explained.

In a phase I trial also reported at this year’s ASCO meeting, 72% of 54 patients with relapsed/refractory CLL treated with single agent idelalisib had a partial response, with a 1-month median time to response and a response duration of 16-plus months, reported Dr. Jennifer R. Brown, director of the Chronic Lymphocytic Leukemia Center at the Dana-Farber Cancer Institute in Boston.

In the phase II study conducted by Dr. O’Brien, patients aged 65 years and older with previously untreated CLL were given idelalisib 150 mg twice daily for 48 weeks and rituximab 375 mg/m² once weekly for 8 weeks. Disease status was determined by investigators. Those patients who did not have disease progression after 48 weeks were allowed to stay on therapy in an extension study.

In the primary study, 62 of 64 patients completed the 8 weeks of therapy with rituximab and idelalisib, and 43 completed all 48 weeks. Of the 21 who discontinued therapy, 17 did so because of adverse events, 3 died, and 1 withdrew consent. Of 40 patients enrolled in the extension phase of the trial, 33 were still on study as of May 2013. Of the 7 patients who withdrew from the extension study, 6 did so because of adverse events and 1 withdrew consent.

Of the 64 patients started on the drug combination in the primary study, 12 had a complete response, and 3 of these patients had a 17p deletion and/or TP53 mutation. Partial responses occurred in 50 patients, 6 of whom had mutations or deletions.

In all, 23% of patients in the primary and extension studies had grade 3 diarrhea and/or colitis. Grade 3 or greater pneumonia occurred in 17%, transaminase elevations in 23%, and neutropenia in 28%. Of the patients who discontinued therapy due to adverse events, 5 did so because of respiratory events in the first 24 weeks, and 5 did so because of diarrhea/colitis during the extension study. Other causes of discontinuation were anemia and elevated transaminases.

The study was sponsored by Gilead Sciences. Dr. O’Brien disclosed receiving research funding from the company. Dr. Brown reported having no relevant financial disclosures.

CHICAGO – When paired with rituximab, the experimental agent idelalisib was associated with durable progression-free survival rates in older patients with treatment-naive chronic lymphocytic leukemia or small lymphocytic lymphoma, Dr. Susan M. O’Brien reported at the annual meeting of the American Society of Clinical Oncology.

Among 64 patients in an open-label phase II study, the overall response rate was 97%, consisting of 19% complete responses and 78% partial responses. Among 9 patients with chromosome 17 abnormalities, which are associated with a poor prognosis, 3 had a complete response and 6 had a partial response, said Dr. O’Brien, of the University of Texas MD Anderson Cancer Center in Houston.

Progression-free survival (PFS) at 24 months was 93% among all patients, and 100% among the 9 patients with the poor-prognosis TP53 mutation or a deletion in chromosome 17 (17p).

"I think that these data, particularly the PFS, really support further evaluation of this agent in front-line CLL [chronic lymphocytic leukemia]," she said.

Idelalisib (GS-1101) is a targeted, highly selective oral inhibitor of the P13 kinase delta isoform (P13K-delta). The oral drug inhibits proliferation of many B-cell malignancies and induces apoptosis, and it inhibits homing and retention of malignant B cells in lymphoid tissues, Dr. O’Brien explained.

In a phase I trial also reported at this year’s ASCO meeting, 72% of 54 patients with relapsed/refractory CLL treated with single agent idelalisib had a partial response, with a 1-month median time to response and a response duration of 16-plus months, reported Dr. Jennifer R. Brown, director of the Chronic Lymphocytic Leukemia Center at the Dana-Farber Cancer Institute in Boston.

In the phase II study conducted by Dr. O’Brien, patients aged 65 years and older with previously untreated CLL were given idelalisib 150 mg twice daily for 48 weeks and rituximab 375 mg/m² once weekly for 8 weeks. Disease status was determined by investigators. Those patients who did not have disease progression after 48 weeks were allowed to stay on therapy in an extension study.

In the primary study, 62 of 64 patients completed the 8 weeks of therapy with rituximab and idelalisib, and 43 completed all 48 weeks. Of the 21 who discontinued therapy, 17 did so because of adverse events, 3 died, and 1 withdrew consent. Of 40 patients enrolled in the extension phase of the trial, 33 were still on study as of May 2013. Of the 7 patients who withdrew from the extension study, 6 did so because of adverse events and 1 withdrew consent.

Of the 64 patients started on the drug combination in the primary study, 12 had a complete response, and 3 of these patients had a 17p deletion and/or TP53 mutation. Partial responses occurred in 50 patients, 6 of whom had mutations or deletions.

In all, 23% of patients in the primary and extension studies had grade 3 diarrhea and/or colitis. Grade 3 or greater pneumonia occurred in 17%, transaminase elevations in 23%, and neutropenia in 28%. Of the patients who discontinued therapy due to adverse events, 5 did so because of respiratory events in the first 24 weeks, and 5 did so because of diarrhea/colitis during the extension study. Other causes of discontinuation were anemia and elevated transaminases.

The study was sponsored by Gilead Sciences. Dr. O’Brien disclosed receiving research funding from the company. Dr. Brown reported having no relevant financial disclosures.

ORLANDO – An investigational immunomodulator prosaically named DIMS 0150 was associated with sustained remissions in some patients with ulcerative colitis, reported investigators at the annual Digestive Disease Week.

Among patients with ulcerative colitis (UC) randomized to receive a single rectally delivered dose of DIMS 0150 or placebo, 5 of 16 patients available for 3-month follow-up had a sustained clinical response, compared with none of the eight control patients who received a placebo enema, said Dr. Thomas Knittel from InDex Pharmaceuticals in Stockholm.

The drug contains a single-stranded oligonucleotide that acts as a Toll-like receptor 9 (TLR9) agonist by activating TLR9 when the drug is administered to mucosal surfaces. TLR9 (also called CD289) encodes a protein involved in innate immunity and pathogen recognition and in mediation of anti-inflammatory cytokines, primarily interleukin 10 and interferon-alpha.

In animal studies, activation of TLR9 has been shown to promote healing of UC.

The investigators conducted a randomized, double-blind, placebo-controlled trial of the agent in patients with UC refractory to steroids. A total of 34 patients were randomized to receive on a 2:1 basis (22:12) either a single 30-mg dose of DIMS 0150 delivered via enema, or a placebo enema consisting of only water.

The patients had Disease Activity Index (DAI) scores of 6-11 pts were taking at least 5 mg steroids/day and were judged as either steroid dependent or steroid resistant.

At the end of the first follow-up week, 7 of 17 patients on DIMS 0150 had a clinical response (decrease in DAI score of at least 3 points from baseline), compared with 1 of 11 patients on placebo. By week 4, two additional patients on the TLR9 agonist had achieved a clinical response (9 of 17), as did three additional patients on placebo (4 of 11).

By week 12, 5 of 16 patients who had received DIMS 0150 and completed 12 weeks of therapy still had a clinical response, in contrast to none of the eight patients on placebo who completed 12 weeks of follow-up. However, neither the 4-week nor 12-week follow-up differences in sustained response between the active drug and placebo groups were significant.

Two of 17 patients on DIMS 0150 had a clinical remission (total DAI score of 2 points or less, with no individual subscore higher than 1) at week 1, 3 of 17 were in remission at week 4, and 6 of 16 were in remission at 12 weeks. In contrast, none of the control patients had remissions at either week 1 or week 4, but two of eight controls were in remission at week 12.

The authors also looked at histologic remission (improvement to a score of 0) at all three time points and found that at week 4, 6 of 17 patients on the TLR9 agonist had a remission, vs. 0 of 11 on placebo, a difference that teetered on the edge of statistical significance (P = .055).

Dr. Knittel did not present safety data, but said that in previous studies, the drug at the 30-mg dose has been shown to be safe and that patients tolerated it well.

In response to a question following his presentation, Dr. Knittel noted that the investigators had not measured cytokine levels to determine whether the drug was having its intended effect, but instead relied on clinical findings to determine efficacy.

The phase II study Dr. Knittel presented confirms clinical data obtained in earlier studies of this agent, and "indicates that a single dose of a TLR9 agonist can be effective, and efficacy was observed with respect to clinical response, clinical remission, and histological healing," he said.

But a gastroenterologist who was not involved in the study says that it was lacking data in several key areas, because the investigators did not measure baseline or post-treatment levels of anti-inflammatory cytokines or C-reactive protein and did not perform endoscopies to assess colonic mucosa.

"In ulcerative colitis, that’s where the rubber hits the road: whether the mucosa gets better," said Dr. Maria T. Abreu, chief of gastroenterology and professor of medicine at the University of Miami.

"I don’t expect it to completely resolve, because even in studies of anti-TNF [tumor necrosis factor–alpha], which we believe to be the most potent therapy we have now for mucosal healing, the numbers of patients that actually have the mucosa heal completely in ulcerative colitis is low – only about a quarter of patients have that happen. ... But these investigators didn’t report any change in the endoscopy," Dr. Abreu said.

The study was funded by InDex Pharmaceuticals. Dr. Knittel is chief medical officer and consultant for the company, and two of his coauthors are employees.

ORLANDO – An investigational immunomodulator prosaically named DIMS 0150 was associated with sustained remissions in some patients with ulcerative colitis, reported investigators at the annual Digestive Disease Week.

Among patients with ulcerative colitis (UC) randomized to receive a single rectally delivered dose of DIMS 0150 or placebo, 5 of 16 patients available for 3-month follow-up had a sustained clinical response, compared with none of the eight control patients who received a placebo enema, said Dr. Thomas Knittel from InDex Pharmaceuticals in Stockholm.

The drug contains a single-stranded oligonucleotide that acts as a Toll-like receptor 9 (TLR9) agonist by activating TLR9 when the drug is administered to mucosal surfaces. TLR9 (also called CD289) encodes a protein involved in innate immunity and pathogen recognition and in mediation of anti-inflammatory cytokines, primarily interleukin 10 and interferon-alpha.

In animal studies, activation of TLR9 has been shown to promote healing of UC.

The investigators conducted a randomized, double-blind, placebo-controlled trial of the agent in patients with UC refractory to steroids. A total of 34 patients were randomized to receive on a 2:1 basis (22:12) either a single 30-mg dose of DIMS 0150 delivered via enema, or a placebo enema consisting of only water.

The patients had Disease Activity Index (DAI) scores of 6-11 pts were taking at least 5 mg steroids/day and were judged as either steroid dependent or steroid resistant.

At the end of the first follow-up week, 7 of 17 patients on DIMS 0150 had a clinical response (decrease in DAI score of at least 3 points from baseline), compared with 1 of 11 patients on placebo. By week 4, two additional patients on the TLR9 agonist had achieved a clinical response (9 of 17), as did three additional patients on placebo (4 of 11).

By week 12, 5 of 16 patients who had received DIMS 0150 and completed 12 weeks of therapy still had a clinical response, in contrast to none of the eight patients on placebo who completed 12 weeks of follow-up. However, neither the 4-week nor 12-week follow-up differences in sustained response between the active drug and placebo groups were significant.

Two of 17 patients on DIMS 0150 had a clinical remission (total DAI score of 2 points or less, with no individual subscore higher than 1) at week 1, 3 of 17 were in remission at week 4, and 6 of 16 were in remission at 12 weeks. In contrast, none of the control patients had remissions at either week 1 or week 4, but two of eight controls were in remission at week 12.

The authors also looked at histologic remission (improvement to a score of 0) at all three time points and found that at week 4, 6 of 17 patients on the TLR9 agonist had a remission, vs. 0 of 11 on placebo, a difference that teetered on the edge of statistical significance (P = .055).

Dr. Knittel did not present safety data, but said that in previous studies, the drug at the 30-mg dose has been shown to be safe and that patients tolerated it well.

In response to a question following his presentation, Dr. Knittel noted that the investigators had not measured cytokine levels to determine whether the drug was having its intended effect, but instead relied on clinical findings to determine efficacy.

The phase II study Dr. Knittel presented confirms clinical data obtained in earlier studies of this agent, and "indicates that a single dose of a TLR9 agonist can be effective, and efficacy was observed with respect to clinical response, clinical remission, and histological healing," he said.

But a gastroenterologist who was not involved in the study says that it was lacking data in several key areas, because the investigators did not measure baseline or post-treatment levels of anti-inflammatory cytokines or C-reactive protein and did not perform endoscopies to assess colonic mucosa.

"In ulcerative colitis, that’s where the rubber hits the road: whether the mucosa gets better," said Dr. Maria T. Abreu, chief of gastroenterology and professor of medicine at the University of Miami.

"I don’t expect it to completely resolve, because even in studies of anti-TNF [tumor necrosis factor–alpha], which we believe to be the most potent therapy we have now for mucosal healing, the numbers of patients that actually have the mucosa heal completely in ulcerative colitis is low – only about a quarter of patients have that happen. ... But these investigators didn’t report any change in the endoscopy," Dr. Abreu said.

The study was funded by InDex Pharmaceuticals. Dr. Knittel is chief medical officer and consultant for the company, and two of his coauthors are employees.

ORLANDO – An investigational immunomodulator prosaically named DIMS 0150 was associated with sustained remissions in some patients with ulcerative colitis, reported investigators at the annual Digestive Disease Week.

Among patients with ulcerative colitis (UC) randomized to receive a single rectally delivered dose of DIMS 0150 or placebo, 5 of 16 patients available for 3-month follow-up had a sustained clinical response, compared with none of the eight control patients who received a placebo enema, said Dr. Thomas Knittel from InDex Pharmaceuticals in Stockholm.

The drug contains a single-stranded oligonucleotide that acts as a Toll-like receptor 9 (TLR9) agonist by activating TLR9 when the drug is administered to mucosal surfaces. TLR9 (also called CD289) encodes a protein involved in innate immunity and pathogen recognition and in mediation of anti-inflammatory cytokines, primarily interleukin 10 and interferon-alpha.

In animal studies, activation of TLR9 has been shown to promote healing of UC.

The investigators conducted a randomized, double-blind, placebo-controlled trial of the agent in patients with UC refractory to steroids. A total of 34 patients were randomized to receive on a 2:1 basis (22:12) either a single 30-mg dose of DIMS 0150 delivered via enema, or a placebo enema consisting of only water.

The patients had Disease Activity Index (DAI) scores of 6-11 pts were taking at least 5 mg steroids/day and were judged as either steroid dependent or steroid resistant.

At the end of the first follow-up week, 7 of 17 patients on DIMS 0150 had a clinical response (decrease in DAI score of at least 3 points from baseline), compared with 1 of 11 patients on placebo. By week 4, two additional patients on the TLR9 agonist had achieved a clinical response (9 of 17), as did three additional patients on placebo (4 of 11).

By week 12, 5 of 16 patients who had received DIMS 0150 and completed 12 weeks of therapy still had a clinical response, in contrast to none of the eight patients on placebo who completed 12 weeks of follow-up. However, neither the 4-week nor 12-week follow-up differences in sustained response between the active drug and placebo groups were significant.

Two of 17 patients on DIMS 0150 had a clinical remission (total DAI score of 2 points or less, with no individual subscore higher than 1) at week 1, 3 of 17 were in remission at week 4, and 6 of 16 were in remission at 12 weeks. In contrast, none of the control patients had remissions at either week 1 or week 4, but two of eight controls were in remission at week 12.

The authors also looked at histologic remission (improvement to a score of 0) at all three time points and found that at week 4, 6 of 17 patients on the TLR9 agonist had a remission, vs. 0 of 11 on placebo, a difference that teetered on the edge of statistical significance (P = .055).

Dr. Knittel did not present safety data, but said that in previous studies, the drug at the 30-mg dose has been shown to be safe and that patients tolerated it well.

In response to a question following his presentation, Dr. Knittel noted that the investigators had not measured cytokine levels to determine whether the drug was having its intended effect, but instead relied on clinical findings to determine efficacy.

The phase II study Dr. Knittel presented confirms clinical data obtained in earlier studies of this agent, and "indicates that a single dose of a TLR9 agonist can be effective, and efficacy was observed with respect to clinical response, clinical remission, and histological healing," he said.

But a gastroenterologist who was not involved in the study says that it was lacking data in several key areas, because the investigators did not measure baseline or post-treatment levels of anti-inflammatory cytokines or C-reactive protein and did not perform endoscopies to assess colonic mucosa.

"In ulcerative colitis, that’s where the rubber hits the road: whether the mucosa gets better," said Dr. Maria T. Abreu, chief of gastroenterology and professor of medicine at the University of Miami.

"I don’t expect it to completely resolve, because even in studies of anti-TNF [tumor necrosis factor–alpha], which we believe to be the most potent therapy we have now for mucosal healing, the numbers of patients that actually have the mucosa heal completely in ulcerative colitis is low – only about a quarter of patients have that happen. ... But these investigators didn’t report any change in the endoscopy," Dr. Abreu said.

The study was funded by InDex Pharmaceuticals. Dr. Knittel is chief medical officer and consultant for the company, and two of his coauthors are employees.

ORLANDO – In a case of nothing being better than something, mesalamine granules proved to be less effective than placebo at preventing the recurrence of diverticulitis, an investigator reported at the annual Digestive Disease Week.

Among 333 patients with diverticulitis in an intention-to-treat population, 67.9% of patients randomly assigned to mesalamine granules (Salofalk) had 48 relapse-free weeks of follow-up, compared with 74.4% of patients assigned to placebo. This difference was not significant, but in a per-protocol population, placebo was significantly better (P = .018), said lead investigator Dr. Wolfgang Kruis from the University of Cologne, Germany.

The trial was stopped early after an interim analysis showed no benefit for mesalamine.

"The results of this trial do not support the use of mesalamine for the maintenance of relapse-free diverticular disease," Dr. Kruis said.

Mesalamine, whose chemical name is 5-aminosalicylic acid (5-ASA), appeared to have no effect on biomarkers of inflammation, but the therapy was safe and was not associated with unexpected adverse events, he noted.

Mesalamine and other 5-ASA drugs are commonly prescribed to treat ulcerative colitis, and previous open-label studies have shown clinical benefit of these agents in patients with recurrent diverticulitis, Dr. Kruis said.

To see whether those findings would stand up to a more rigorous randomized, double-blind, controlled trial, he and his colleagues from 57 centers in 11 countries compared mesalamine granules delivered 3 g by mouth daily to placebo in 333 patients (165 assigned to mesalamine and 168 to placebo) for whom complete information was available (the full-analysis population). A total of 270 patients completed the 48 weeks of therapy, 133 of whom were assigned to mesalamine and 137 to placebo (the per-protocol population).

As noted before, numerically but not significantly more patients on placebo in the full-analysis population were recurrence free at 48 weeks, where recurrence was defined as a C-reactive protein (CRP) level above the upper limit of normal, or leukocytosis plus the presence of diverticulitis-like clinical signs plus typical findings on CT scans or ultrasound.

But in the per-protocol analysis, 78.9% of patients on the 5-ASA agent had no recurrent diverticulitis after 48 weeks, compared with 89.8% of placebo-treated controls (P = .018).

There was no significant difference in mean time in days to recurrence, mean erythrocyte sedimentation rate, mean CRP levels, or mean leukocytosis throughout the study.

"It really was remarkable that [patients on mesalamine] did worse," commented Dr. Nicholas J. Talley from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In an interview, Dr. Talley speculated that the difference seen in the per-protocol analysis suggests that "perhaps suppressing inflammation in this setting actually sets up a different cascade for some reason that makes people worse."

Dr. Talley noted that the authors did not perform baseline colonic biopsies, and it is possible that there was some undetected heterogeneity in the population that might explain the lack of a benefit from the active drug.

"Diverticular disease and diverticulitis are probably not one entity," he said.

The study was funded by Dr. Falk Pharma. Dr. Kruis disclosed receiving speaking and teaching fees from the company, and three of his coauthors are company employees.

ORLANDO – In a case of nothing being better than something, mesalamine granules proved to be less effective than placebo at preventing the recurrence of diverticulitis, an investigator reported at the annual Digestive Disease Week.

Among 333 patients with diverticulitis in an intention-to-treat population, 67.9% of patients randomly assigned to mesalamine granules (Salofalk) had 48 relapse-free weeks of follow-up, compared with 74.4% of patients assigned to placebo. This difference was not significant, but in a per-protocol population, placebo was significantly better (P = .018), said lead investigator Dr. Wolfgang Kruis from the University of Cologne, Germany.

The trial was stopped early after an interim analysis showed no benefit for mesalamine.

"The results of this trial do not support the use of mesalamine for the maintenance of relapse-free diverticular disease," Dr. Kruis said.

Mesalamine, whose chemical name is 5-aminosalicylic acid (5-ASA), appeared to have no effect on biomarkers of inflammation, but the therapy was safe and was not associated with unexpected adverse events, he noted.

Mesalamine and other 5-ASA drugs are commonly prescribed to treat ulcerative colitis, and previous open-label studies have shown clinical benefit of these agents in patients with recurrent diverticulitis, Dr. Kruis said.

To see whether those findings would stand up to a more rigorous randomized, double-blind, controlled trial, he and his colleagues from 57 centers in 11 countries compared mesalamine granules delivered 3 g by mouth daily to placebo in 333 patients (165 assigned to mesalamine and 168 to placebo) for whom complete information was available (the full-analysis population). A total of 270 patients completed the 48 weeks of therapy, 133 of whom were assigned to mesalamine and 137 to placebo (the per-protocol population).

As noted before, numerically but not significantly more patients on placebo in the full-analysis population were recurrence free at 48 weeks, where recurrence was defined as a C-reactive protein (CRP) level above the upper limit of normal, or leukocytosis plus the presence of diverticulitis-like clinical signs plus typical findings on CT scans or ultrasound.

But in the per-protocol analysis, 78.9% of patients on the 5-ASA agent had no recurrent diverticulitis after 48 weeks, compared with 89.8% of placebo-treated controls (P = .018).

There was no significant difference in mean time in days to recurrence, mean erythrocyte sedimentation rate, mean CRP levels, or mean leukocytosis throughout the study.

"It really was remarkable that [patients on mesalamine] did worse," commented Dr. Nicholas J. Talley from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In an interview, Dr. Talley speculated that the difference seen in the per-protocol analysis suggests that "perhaps suppressing inflammation in this setting actually sets up a different cascade for some reason that makes people worse."

Dr. Talley noted that the authors did not perform baseline colonic biopsies, and it is possible that there was some undetected heterogeneity in the population that might explain the lack of a benefit from the active drug.

"Diverticular disease and diverticulitis are probably not one entity," he said.

The study was funded by Dr. Falk Pharma. Dr. Kruis disclosed receiving speaking and teaching fees from the company, and three of his coauthors are company employees.

ORLANDO – In a case of nothing being better than something, mesalamine granules proved to be less effective than placebo at preventing the recurrence of diverticulitis, an investigator reported at the annual Digestive Disease Week.

Among 333 patients with diverticulitis in an intention-to-treat population, 67.9% of patients randomly assigned to mesalamine granules (Salofalk) had 48 relapse-free weeks of follow-up, compared with 74.4% of patients assigned to placebo. This difference was not significant, but in a per-protocol population, placebo was significantly better (P = .018), said lead investigator Dr. Wolfgang Kruis from the University of Cologne, Germany.

The trial was stopped early after an interim analysis showed no benefit for mesalamine.

"The results of this trial do not support the use of mesalamine for the maintenance of relapse-free diverticular disease," Dr. Kruis said.

Mesalamine, whose chemical name is 5-aminosalicylic acid (5-ASA), appeared to have no effect on biomarkers of inflammation, but the therapy was safe and was not associated with unexpected adverse events, he noted.

Mesalamine and other 5-ASA drugs are commonly prescribed to treat ulcerative colitis, and previous open-label studies have shown clinical benefit of these agents in patients with recurrent diverticulitis, Dr. Kruis said.

To see whether those findings would stand up to a more rigorous randomized, double-blind, controlled trial, he and his colleagues from 57 centers in 11 countries compared mesalamine granules delivered 3 g by mouth daily to placebo in 333 patients (165 assigned to mesalamine and 168 to placebo) for whom complete information was available (the full-analysis population). A total of 270 patients completed the 48 weeks of therapy, 133 of whom were assigned to mesalamine and 137 to placebo (the per-protocol population).

As noted before, numerically but not significantly more patients on placebo in the full-analysis population were recurrence free at 48 weeks, where recurrence was defined as a C-reactive protein (CRP) level above the upper limit of normal, or leukocytosis plus the presence of diverticulitis-like clinical signs plus typical findings on CT scans or ultrasound.

But in the per-protocol analysis, 78.9% of patients on the 5-ASA agent had no recurrent diverticulitis after 48 weeks, compared with 89.8% of placebo-treated controls (P = .018).

There was no significant difference in mean time in days to recurrence, mean erythrocyte sedimentation rate, mean CRP levels, or mean leukocytosis throughout the study.

"It really was remarkable that [patients on mesalamine] did worse," commented Dr. Nicholas J. Talley from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In an interview, Dr. Talley speculated that the difference seen in the per-protocol analysis suggests that "perhaps suppressing inflammation in this setting actually sets up a different cascade for some reason that makes people worse."

Dr. Talley noted that the authors did not perform baseline colonic biopsies, and it is possible that there was some undetected heterogeneity in the population that might explain the lack of a benefit from the active drug.

"Diverticular disease and diverticulitis are probably not one entity," he said.

The study was funded by Dr. Falk Pharma. Dr. Kruis disclosed receiving speaking and teaching fees from the company, and three of his coauthors are company employees.

ORLANDO – Guidelines that attempt to predict whether stones have migrated into the common bile duct appear to get it right, said an investigator at the annual Digestive Disease Week.

A prospective study looking at American Society for Gastrointestinal Endoscopy (ASGE) criteria for evaluating patients with choledocholithiais found that the guidelines correctly predicted the presence of a common bile duct (CBD) stone in 75% of patients deemed to be at high risk, and accurately called the shots in 55% of patients at intermediate risk, reported Dr. Andrew Korson of Beth Israel Deaconess Medical Center in Boston.

The ASGE guidelines are intended to help clinicians decide whether and when an invasive procedure may be warranted, based on certain clinical features, Dr. Korson noted.

"In the past decade there has been heightened awareness of the problem of proper patient selection for endoscopic retrograde cholangiography [ERC] in the setting of suspected choledocholithiasis, and to date there has been no single noninvasive test that has been shown to reliably identify these patients," he said.

The ASGE guidelines stratify patients into high-risk (greater than 50% incidence of choledocholithiasis), intermediate-risk (10%-50% incidence), and low-risk (less than 10% incidence) categories based on the presence of specific predictive features.

Very strong predictors of choledocholithiasis are evidence of a CBD stone on transabdominal ultrasound, clinical ascending cholangitis, and a bilirubin level higher than 4 mg/dL. Strong predictors are a dilated CBD on ultrasound (greater than 6 mm with gallbladder in situ) and a bilirubin level from 1.8 to 4 mg/dL. Moderate predictors are an abnormal liver biochemical test other than bilirubin, age older than 55, and clinical gallstone pancreatitis.

High-risk patients under this classification scheme are those with any very strong predictor or both strong predictors. Patients at low risk are those with no predictors present, and those at intermediate risk are everyone in between.

Only some get stones

Dr. Korson and his colleagues looked at the proportion of patients within ASGE risk categories who actually had choledocholithiasis on ERC.

They enrolled 402 consecutive patients referred to the hospital for ERC for suspected choledocholithiasis.

They considered clinical, radiographic, and biochemical data at initial presentation, and used transabdominal ultrasound to measure the CBD diameter and the presence of echodensities suggestive of stones or, if ultrasound was not performed, CT or magnetic resonance cholangiopancreatography (MRCP) to gather evidence for choledocholithiasis.

The authors used the data to prospectively apply ASGE criteria and risk-stratify the patients.

Endoscopy was performed with either sphincterectomy or balloon sweep at the discretion of the attending gastroenterologist, with the endoscopist blinded to the risk category.

Of the 402 patients enrolled, 69 were excluded for anatomical reasons or because of a lack of complete data, leaving 333 for the final analysis.

Of the 243 patients classified as high risk, 183 (75.3%) were found to have a CBD stone, and 60 (24.7%) had no stone. Of the 88 at intermediate risk, 47 (53.4%) were found on ERC to have a stone, and 41 (46.6%) were not. Neither of the two low-risk patients had a stone.

The investigators determined the positive predictive value (PPV) of the ASGE criteria to be 55% for intermediate-risk patients, and 75% for high-risk patients (P for each less than .001).

In both univariate and multivariate analyses, only radiographic evidence of a CBD stone and elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) were significant predictors of risk. Ascending cholangitis, a total bilirubin level above 4 mg/dL, dilated common bile duct, age, and gallstone pancreatitis were not significant independent predictors.

The odds ratio (OR) for choledocholithiasis based on CBD stone on radiographic evidence was 3.56 (P less than .001), and for elevated liver biochemical tests, was 2.26 (P = .03).

In a post hoc univariate analysis, each 10-IU/L increase in ALT, AST, and alkaline phosphatase was associated with a respective odds ratio of 1.01 (P = .04), 1.01 (P =.03), and 1.02 (P = .04) for choledocholithiasis.

Dr. Korson noted that based on the heavy weighting of their sample toward high- and intermediate-risk patients, "further evaluation of factors that separate intermediate- from low-risk patients is warranted."

He acknowledged study limitations, including possible referral bias, because all of the cases were evaluated at a tertiary care center, a high-acuity study population was used, and CT or MRCP was used to detect CBD dilation or a stone when ultrasound was unavailable.

The funding source for the study was not disclosed. Dr. Korson reported having no relevant financial disclosures.

ORLANDO – Guidelines that attempt to predict whether stones have migrated into the common bile duct appear to get it right, said an investigator at the annual Digestive Disease Week.

A prospective study looking at American Society for Gastrointestinal Endoscopy (ASGE) criteria for evaluating patients with choledocholithiais found that the guidelines correctly predicted the presence of a common bile duct (CBD) stone in 75% of patients deemed to be at high risk, and accurately called the shots in 55% of patients at intermediate risk, reported Dr. Andrew Korson of Beth Israel Deaconess Medical Center in Boston.

The ASGE guidelines are intended to help clinicians decide whether and when an invasive procedure may be warranted, based on certain clinical features, Dr. Korson noted.

"In the past decade there has been heightened awareness of the problem of proper patient selection for endoscopic retrograde cholangiography [ERC] in the setting of suspected choledocholithiasis, and to date there has been no single noninvasive test that has been shown to reliably identify these patients," he said.

The ASGE guidelines stratify patients into high-risk (greater than 50% incidence of choledocholithiasis), intermediate-risk (10%-50% incidence), and low-risk (less than 10% incidence) categories based on the presence of specific predictive features.

Very strong predictors of choledocholithiasis are evidence of a CBD stone on transabdominal ultrasound, clinical ascending cholangitis, and a bilirubin level higher than 4 mg/dL. Strong predictors are a dilated CBD on ultrasound (greater than 6 mm with gallbladder in situ) and a bilirubin level from 1.8 to 4 mg/dL. Moderate predictors are an abnormal liver biochemical test other than bilirubin, age older than 55, and clinical gallstone pancreatitis.

High-risk patients under this classification scheme are those with any very strong predictor or both strong predictors. Patients at low risk are those with no predictors present, and those at intermediate risk are everyone in between.

Only some get stones

Dr. Korson and his colleagues looked at the proportion of patients within ASGE risk categories who actually had choledocholithiasis on ERC.

They enrolled 402 consecutive patients referred to the hospital for ERC for suspected choledocholithiasis.

They considered clinical, radiographic, and biochemical data at initial presentation, and used transabdominal ultrasound to measure the CBD diameter and the presence of echodensities suggestive of stones or, if ultrasound was not performed, CT or magnetic resonance cholangiopancreatography (MRCP) to gather evidence for choledocholithiasis.

The authors used the data to prospectively apply ASGE criteria and risk-stratify the patients.

Endoscopy was performed with either sphincterectomy or balloon sweep at the discretion of the attending gastroenterologist, with the endoscopist blinded to the risk category.

Of the 402 patients enrolled, 69 were excluded for anatomical reasons or because of a lack of complete data, leaving 333 for the final analysis.

Of the 243 patients classified as high risk, 183 (75.3%) were found to have a CBD stone, and 60 (24.7%) had no stone. Of the 88 at intermediate risk, 47 (53.4%) were found on ERC to have a stone, and 41 (46.6%) were not. Neither of the two low-risk patients had a stone.

The investigators determined the positive predictive value (PPV) of the ASGE criteria to be 55% for intermediate-risk patients, and 75% for high-risk patients (P for each less than .001).

In both univariate and multivariate analyses, only radiographic evidence of a CBD stone and elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) were significant predictors of risk. Ascending cholangitis, a total bilirubin level above 4 mg/dL, dilated common bile duct, age, and gallstone pancreatitis were not significant independent predictors.

The odds ratio (OR) for choledocholithiasis based on CBD stone on radiographic evidence was 3.56 (P less than .001), and for elevated liver biochemical tests, was 2.26 (P = .03).

In a post hoc univariate analysis, each 10-IU/L increase in ALT, AST, and alkaline phosphatase was associated with a respective odds ratio of 1.01 (P = .04), 1.01 (P =.03), and 1.02 (P = .04) for choledocholithiasis.

Dr. Korson noted that based on the heavy weighting of their sample toward high- and intermediate-risk patients, "further evaluation of factors that separate intermediate- from low-risk patients is warranted."

He acknowledged study limitations, including possible referral bias, because all of the cases were evaluated at a tertiary care center, a high-acuity study population was used, and CT or MRCP was used to detect CBD dilation or a stone when ultrasound was unavailable.

The funding source for the study was not disclosed. Dr. Korson reported having no relevant financial disclosures.

ORLANDO – Guidelines that attempt to predict whether stones have migrated into the common bile duct appear to get it right, said an investigator at the annual Digestive Disease Week.

A prospective study looking at American Society for Gastrointestinal Endoscopy (ASGE) criteria for evaluating patients with choledocholithiais found that the guidelines correctly predicted the presence of a common bile duct (CBD) stone in 75% of patients deemed to be at high risk, and accurately called the shots in 55% of patients at intermediate risk, reported Dr. Andrew Korson of Beth Israel Deaconess Medical Center in Boston.

The ASGE guidelines are intended to help clinicians decide whether and when an invasive procedure may be warranted, based on certain clinical features, Dr. Korson noted.

"In the past decade there has been heightened awareness of the problem of proper patient selection for endoscopic retrograde cholangiography [ERC] in the setting of suspected choledocholithiasis, and to date there has been no single noninvasive test that has been shown to reliably identify these patients," he said.

The ASGE guidelines stratify patients into high-risk (greater than 50% incidence of choledocholithiasis), intermediate-risk (10%-50% incidence), and low-risk (less than 10% incidence) categories based on the presence of specific predictive features.

Very strong predictors of choledocholithiasis are evidence of a CBD stone on transabdominal ultrasound, clinical ascending cholangitis, and a bilirubin level higher than 4 mg/dL. Strong predictors are a dilated CBD on ultrasound (greater than 6 mm with gallbladder in situ) and a bilirubin level from 1.8 to 4 mg/dL. Moderate predictors are an abnormal liver biochemical test other than bilirubin, age older than 55, and clinical gallstone pancreatitis.

High-risk patients under this classification scheme are those with any very strong predictor or both strong predictors. Patients at low risk are those with no predictors present, and those at intermediate risk are everyone in between.

Only some get stones

Dr. Korson and his colleagues looked at the proportion of patients within ASGE risk categories who actually had choledocholithiasis on ERC.

They enrolled 402 consecutive patients referred to the hospital for ERC for suspected choledocholithiasis.

They considered clinical, radiographic, and biochemical data at initial presentation, and used transabdominal ultrasound to measure the CBD diameter and the presence of echodensities suggestive of stones or, if ultrasound was not performed, CT or magnetic resonance cholangiopancreatography (MRCP) to gather evidence for choledocholithiasis.

The authors used the data to prospectively apply ASGE criteria and risk-stratify the patients.

Endoscopy was performed with either sphincterectomy or balloon sweep at the discretion of the attending gastroenterologist, with the endoscopist blinded to the risk category.

Of the 402 patients enrolled, 69 were excluded for anatomical reasons or because of a lack of complete data, leaving 333 for the final analysis.

Of the 243 patients classified as high risk, 183 (75.3%) were found to have a CBD stone, and 60 (24.7%) had no stone. Of the 88 at intermediate risk, 47 (53.4%) were found on ERC to have a stone, and 41 (46.6%) were not. Neither of the two low-risk patients had a stone.

The investigators determined the positive predictive value (PPV) of the ASGE criteria to be 55% for intermediate-risk patients, and 75% for high-risk patients (P for each less than .001).

In both univariate and multivariate analyses, only radiographic evidence of a CBD stone and elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) were significant predictors of risk. Ascending cholangitis, a total bilirubin level above 4 mg/dL, dilated common bile duct, age, and gallstone pancreatitis were not significant independent predictors.

The odds ratio (OR) for choledocholithiasis based on CBD stone on radiographic evidence was 3.56 (P less than .001), and for elevated liver biochemical tests, was 2.26 (P = .03).

In a post hoc univariate analysis, each 10-IU/L increase in ALT, AST, and alkaline phosphatase was associated with a respective odds ratio of 1.01 (P = .04), 1.01 (P =.03), and 1.02 (P = .04) for choledocholithiasis.

Dr. Korson noted that based on the heavy weighting of their sample toward high- and intermediate-risk patients, "further evaluation of factors that separate intermediate- from low-risk patients is warranted."

He acknowledged study limitations, including possible referral bias, because all of the cases were evaluated at a tertiary care center, a high-acuity study population was used, and CT or MRCP was used to detect CBD dilation or a stone when ultrasound was unavailable.

The funding source for the study was not disclosed. Dr. Korson reported having no relevant financial disclosures.

ORLANDO – Home monitoring of select patients with mild, nonalcoholic acute interstitial pancreatitis is as safe as in-hospital monitoring, at a cost saving of nearly $15,000, according to a study presented at the annual Digestive Disease Week.

In a randomized controlled trial of 84 patients there were no cases of organ failure or pancreatic necrosis and no deaths within 30 days in patients assigned to either home or hospital monitoring. One patient in the home group and two in the hospital group required readmission within 30 days of discharge, reported Dr. Ali T. Ince of the Bezmialem Vakif University Medical Faculty Hospital in Istanbul, Turkey.

The total tab for home monitoring, including emergency department evaluation, intravenous therapy, and nursing visits, was $7,135, compared with $21,960 for in-hospital care, a savings of $14,825.

"Patients with mild nonalcoholic acute pancreatitis can be safely treated at home with regular visits by a nurse. Widespread adoption of this practice could result in large costs savings," Dr. Ince said.

In 2009, acute pancreatitis cases cost the U.S. health care system about $2.6 billion, for a median per patient charge of $6,096.

"The cost of severe acute pancreatitis is more than the cost of mild acute pancreatitis. However, since only 10%-15% of patients have severe acute pancreatitis, the majority of patients admitted have mild disease," he noted.

To see whether home care of such patients could be safely provided, the investigators enrolled patients admitted to the emergency department for evaluation of acute pancreatitis. Those with an Imrie scoring system value of 5 or lower, a Harmless Acute Pancreatitis Score (HAPS) of 2 or less, and a hematocrit of less than 44% were randomly assigned to either home or hospital monitoring, 42 patients in each group. All patients took nothing by mouth initially and had an oral diet gradually reintroduced.

Hospitalized patients were followed for a mean of 5 days. Home-treated patients received nurse visits on the second, third, and fifth day following discharge from the emergency department. At each home visit, nurses took vital signs, assessed symptoms, and evaluated patients’ general condition and transmitted the data to the attending physician. All patients were asked about their complaints and had physical and laboratory exams on day 7, day 14, and day 30.

Patients with organ failure, signs or symptoms of sepsis, alcoholic acute pancreatitis, prior evidence of a dilated pancreatic duct or pancreatic calcifications, coagulopathies, or comorbidities requiring hospitalization were excluded, Dr. Ince said.

All patients in each group were treated with lactated Ringer’s solution 100-150 mL/hour IV for 3 days, parenteral pantoprazole 40 mg/day, intramuscular diclofenac as needed for pain, and parenteral metoclopramide as needed for nausea, he noted.

In addition, those patients with acute biliary pancreatitis and concurrent cholangitis underwent endoscopic retrograde cholangiopancreatography (ERCP) within 12 hours of admission and received oral amoxicillin/clavulanate 875 mg/125 mg and ciprofloxacin 500 mg; they were monitored as inpatients for up to 24 hours following admission. Patients in this group who remained clinically stable with blood cultures negative for pathogenic organisms within the first 24 hours were then randomized.

All patients with acute biliary pancreatitis and an intact gallbladder underwent cholecystectomy within 6 weeks of the pancreatitis episode.

No home-monitored patients required hospitalization in the 5-7 days after discharge, and, as noted before, only one required readmission within 30 days, Dr. Ince said.

He said that the study was limited by the exclusion of alcoholic pancreatitis, which may make the results less applicable to Western nations where alcohol consumption is heavier than in Turkey. He added, however, that acute biliary pancreatitis has overtaken alcoholic pancreatitis in many Western countries, probably because of rising obesity rates.

The study was sponsored by Bezmialem Vakif University. Dr. Ince reported having no financial disclosures.

ORLANDO – Home monitoring of select patients with mild, nonalcoholic acute interstitial pancreatitis is as safe as in-hospital monitoring, at a cost saving of nearly $15,000, according to a study presented at the annual Digestive Disease Week.

In a randomized controlled trial of 84 patients there were no cases of organ failure or pancreatic necrosis and no deaths within 30 days in patients assigned to either home or hospital monitoring. One patient in the home group and two in the hospital group required readmission within 30 days of discharge, reported Dr. Ali T. Ince of the Bezmialem Vakif University Medical Faculty Hospital in Istanbul, Turkey.

The total tab for home monitoring, including emergency department evaluation, intravenous therapy, and nursing visits, was $7,135, compared with $21,960 for in-hospital care, a savings of $14,825.

"Patients with mild nonalcoholic acute pancreatitis can be safely treated at home with regular visits by a nurse. Widespread adoption of this practice could result in large costs savings," Dr. Ince said.

In 2009, acute pancreatitis cases cost the U.S. health care system about $2.6 billion, for a median per patient charge of $6,096.

"The cost of severe acute pancreatitis is more than the cost of mild acute pancreatitis. However, since only 10%-15% of patients have severe acute pancreatitis, the majority of patients admitted have mild disease," he noted.

To see whether home care of such patients could be safely provided, the investigators enrolled patients admitted to the emergency department for evaluation of acute pancreatitis. Those with an Imrie scoring system value of 5 or lower, a Harmless Acute Pancreatitis Score (HAPS) of 2 or less, and a hematocrit of less than 44% were randomly assigned to either home or hospital monitoring, 42 patients in each group. All patients took nothing by mouth initially and had an oral diet gradually reintroduced.

Hospitalized patients were followed for a mean of 5 days. Home-treated patients received nurse visits on the second, third, and fifth day following discharge from the emergency department. At each home visit, nurses took vital signs, assessed symptoms, and evaluated patients’ general condition and transmitted the data to the attending physician. All patients were asked about their complaints and had physical and laboratory exams on day 7, day 14, and day 30.

Patients with organ failure, signs or symptoms of sepsis, alcoholic acute pancreatitis, prior evidence of a dilated pancreatic duct or pancreatic calcifications, coagulopathies, or comorbidities requiring hospitalization were excluded, Dr. Ince said.

All patients in each group were treated with lactated Ringer’s solution 100-150 mL/hour IV for 3 days, parenteral pantoprazole 40 mg/day, intramuscular diclofenac as needed for pain, and parenteral metoclopramide as needed for nausea, he noted.

In addition, those patients with acute biliary pancreatitis and concurrent cholangitis underwent endoscopic retrograde cholangiopancreatography (ERCP) within 12 hours of admission and received oral amoxicillin/clavulanate 875 mg/125 mg and ciprofloxacin 500 mg; they were monitored as inpatients for up to 24 hours following admission. Patients in this group who remained clinically stable with blood cultures negative for pathogenic organisms within the first 24 hours were then randomized.

All patients with acute biliary pancreatitis and an intact gallbladder underwent cholecystectomy within 6 weeks of the pancreatitis episode.

No home-monitored patients required hospitalization in the 5-7 days after discharge, and, as noted before, only one required readmission within 30 days, Dr. Ince said.

He said that the study was limited by the exclusion of alcoholic pancreatitis, which may make the results less applicable to Western nations where alcohol consumption is heavier than in Turkey. He added, however, that acute biliary pancreatitis has overtaken alcoholic pancreatitis in many Western countries, probably because of rising obesity rates.

The study was sponsored by Bezmialem Vakif University. Dr. Ince reported having no financial disclosures.

ORLANDO – Home monitoring of select patients with mild, nonalcoholic acute interstitial pancreatitis is as safe as in-hospital monitoring, at a cost saving of nearly $15,000, according to a study presented at the annual Digestive Disease Week.

In a randomized controlled trial of 84 patients there were no cases of organ failure or pancreatic necrosis and no deaths within 30 days in patients assigned to either home or hospital monitoring. One patient in the home group and two in the hospital group required readmission within 30 days of discharge, reported Dr. Ali T. Ince of the Bezmialem Vakif University Medical Faculty Hospital in Istanbul, Turkey.

The total tab for home monitoring, including emergency department evaluation, intravenous therapy, and nursing visits, was $7,135, compared with $21,960 for in-hospital care, a savings of $14,825.

"Patients with mild nonalcoholic acute pancreatitis can be safely treated at home with regular visits by a nurse. Widespread adoption of this practice could result in large costs savings," Dr. Ince said.

In 2009, acute pancreatitis cases cost the U.S. health care system about $2.6 billion, for a median per patient charge of $6,096.

"The cost of severe acute pancreatitis is more than the cost of mild acute pancreatitis. However, since only 10%-15% of patients have severe acute pancreatitis, the majority of patients admitted have mild disease," he noted.

To see whether home care of such patients could be safely provided, the investigators enrolled patients admitted to the emergency department for evaluation of acute pancreatitis. Those with an Imrie scoring system value of 5 or lower, a Harmless Acute Pancreatitis Score (HAPS) of 2 or less, and a hematocrit of less than 44% were randomly assigned to either home or hospital monitoring, 42 patients in each group. All patients took nothing by mouth initially and had an oral diet gradually reintroduced.

Hospitalized patients were followed for a mean of 5 days. Home-treated patients received nurse visits on the second, third, and fifth day following discharge from the emergency department. At each home visit, nurses took vital signs, assessed symptoms, and evaluated patients’ general condition and transmitted the data to the attending physician. All patients were asked about their complaints and had physical and laboratory exams on day 7, day 14, and day 30.

Patients with organ failure, signs or symptoms of sepsis, alcoholic acute pancreatitis, prior evidence of a dilated pancreatic duct or pancreatic calcifications, coagulopathies, or comorbidities requiring hospitalization were excluded, Dr. Ince said.

All patients in each group were treated with lactated Ringer’s solution 100-150 mL/hour IV for 3 days, parenteral pantoprazole 40 mg/day, intramuscular diclofenac as needed for pain, and parenteral metoclopramide as needed for nausea, he noted.

In addition, those patients with acute biliary pancreatitis and concurrent cholangitis underwent endoscopic retrograde cholangiopancreatography (ERCP) within 12 hours of admission and received oral amoxicillin/clavulanate 875 mg/125 mg and ciprofloxacin 500 mg; they were monitored as inpatients for up to 24 hours following admission. Patients in this group who remained clinically stable with blood cultures negative for pathogenic organisms within the first 24 hours were then randomized.

All patients with acute biliary pancreatitis and an intact gallbladder underwent cholecystectomy within 6 weeks of the pancreatitis episode.

No home-monitored patients required hospitalization in the 5-7 days after discharge, and, as noted before, only one required readmission within 30 days, Dr. Ince said.

He said that the study was limited by the exclusion of alcoholic pancreatitis, which may make the results less applicable to Western nations where alcohol consumption is heavier than in Turkey. He added, however, that acute biliary pancreatitis has overtaken alcoholic pancreatitis in many Western countries, probably because of rising obesity rates.

The study was sponsored by Bezmialem Vakif University. Dr. Ince reported having no financial disclosures.