TIP promising as first-line germ cell tumor therapy

CHICAGO – The salvage chemotherapy regimen of paclitaxel, ifosfamide, and cisplatin was active in the first-line treatment of intermediate- and poor-risk germ cell tumors in a small multicenter phase II study.

Overall, 28 of 41 evaluable patients achieved a complete response (68%), including 57% of intermediate risk (8/14) and 74% of poor-risk (20/27) patients.

"TIP demonstrated promising efficacy and met its prespecified endpoint as worthy of further study," Dr. Darren Feldman said at the annual meeting of the American Society of Clinical Oncology.

Paclitaxel (Taxol), ifosfamide (Ifex) and cisplatin (Platinol), or TIP, has become a standard regimen for germ cell tumor patients requiring salvage chemotherapy, demonstrating an approximately 70% complete response rate and 63% progression-free survival after a median of 6 years in relapsed patients.

As a result of the findings, a multicenter, randomized phase II trial has been initiated comparing TIP with standard BEP (bleomycin, etoposide, and cisplatin) as first-line therapy in intermediate- and poor-risk patients, said Dr. Feldman, with Memorial Sloan-Kettering Cancer Center in New York.

The current trial enrolled 44 men with germ cell tumors that were International Germ Cell Cancer Collaborative Group (IGCCCG) poor-risk (66%) or modified intermediate-risk, defined by serum lactate dehydrogenase (LDH) three times the upper limit of normal, if LDH was the only intermediate-risk criterion.

Histology was non-seminoma in 86% and the testis was the primary tumor site in 68%. Median patient age was 27 years.

Four cycles of TIP every 21 days was given, as planned, in 89% of patients. The regimen contained paclitaxel 120 mg/m² daily on days 1-2; ifosfamide 1,200 mg/m² mixed 1:1 with Mesna 1,200 mg/m², both daily on days 1-5; and cisplatin 20 mg/m² daily on days 1-5. Peg-filgrastim 6 mg was given subcutaneously as neutropenic fever prophylaxis on day 6 or 7.

An additional one to two cycles of adjuvant TIP could be administered if viable germ cell tumor was found at postchemotherapy surgery. Paclitaxel was initially dosed at 240 mg/m² over 5 days, but the dosing was changed to 2 days because of allergic infusion reactions.

In all, 27 of the 41 patients achieved a complete response to chemotherapy, defined by marker and radiographic normalization or marker normalization with full resection of all tumor masses and pathology revealing teratoma or necrosis, Dr. Feldman said.

One patient achieved a complete response to chemotherapy plus surgery, defined by marker normalization plus full resection with viable germ cell tumor in the specimen, but negative margins.

Partial responses, lasting 4 weeks with negative markers, were observed in 36% of intermediate-risk (5/14) and 4% of poor-risk patients (1/27). Favorable responses (CR plus PR) were seen in 93% and 78%, and incomplete responses in 7% and 22%.

After a median follow-up of 3.1 years, the estimated progression-free survival was 79% overall, 87% among intermediate-risk patients and 76% among poor-risk patients, Dr. Feldman said.

"These results compare favorably to historic results and, in fact, look similar to what would be expected in IGCCCG good- or intermediate-risk patients," he added.

At the time of the analysis, 80% of patients remained progression free and only two had died, resulting in an estimated 3-year overall survival rate of 95%.

TIP had an acceptable safety profile, with no treatment-related deaths and grade 3/4 events limited to hematologic or electrolyte abnormalities, Dr. Feldman said.

Dr. Feldman reported having no financial disclosures. A coauthor reported a consultant/advisory role with Bristol-Myers Squibb.

pwendling@frontlinemedcom.com

CHICAGO – The salvage chemotherapy regimen of paclitaxel, ifosfamide, and cisplatin was active in the first-line treatment of intermediate- and poor-risk germ cell tumors in a small multicenter phase II study.

Overall, 28 of 41 evaluable patients achieved a complete response (68%), including 57% of intermediate risk (8/14) and 74% of poor-risk (20/27) patients.

"TIP demonstrated promising efficacy and met its prespecified endpoint as worthy of further study," Dr. Darren Feldman said at the annual meeting of the American Society of Clinical Oncology.

Paclitaxel (Taxol), ifosfamide (Ifex) and cisplatin (Platinol), or TIP, has become a standard regimen for germ cell tumor patients requiring salvage chemotherapy, demonstrating an approximately 70% complete response rate and 63% progression-free survival after a median of 6 years in relapsed patients.

As a result of the findings, a multicenter, randomized phase II trial has been initiated comparing TIP with standard BEP (bleomycin, etoposide, and cisplatin) as first-line therapy in intermediate- and poor-risk patients, said Dr. Feldman, with Memorial Sloan-Kettering Cancer Center in New York.

The current trial enrolled 44 men with germ cell tumors that were International Germ Cell Cancer Collaborative Group (IGCCCG) poor-risk (66%) or modified intermediate-risk, defined by serum lactate dehydrogenase (LDH) three times the upper limit of normal, if LDH was the only intermediate-risk criterion.

Histology was non-seminoma in 86% and the testis was the primary tumor site in 68%. Median patient age was 27 years.

Four cycles of TIP every 21 days was given, as planned, in 89% of patients. The regimen contained paclitaxel 120 mg/m² daily on days 1-2; ifosfamide 1,200 mg/m² mixed 1:1 with Mesna 1,200 mg/m², both daily on days 1-5; and cisplatin 20 mg/m² daily on days 1-5. Peg-filgrastim 6 mg was given subcutaneously as neutropenic fever prophylaxis on day 6 or 7.

An additional one to two cycles of adjuvant TIP could be administered if viable germ cell tumor was found at postchemotherapy surgery. Paclitaxel was initially dosed at 240 mg/m² over 5 days, but the dosing was changed to 2 days because of allergic infusion reactions.

In all, 27 of the 41 patients achieved a complete response to chemotherapy, defined by marker and radiographic normalization or marker normalization with full resection of all tumor masses and pathology revealing teratoma or necrosis, Dr. Feldman said.

One patient achieved a complete response to chemotherapy plus surgery, defined by marker normalization plus full resection with viable germ cell tumor in the specimen, but negative margins.

Partial responses, lasting 4 weeks with negative markers, were observed in 36% of intermediate-risk (5/14) and 4% of poor-risk patients (1/27). Favorable responses (CR plus PR) were seen in 93% and 78%, and incomplete responses in 7% and 22%.

After a median follow-up of 3.1 years, the estimated progression-free survival was 79% overall, 87% among intermediate-risk patients and 76% among poor-risk patients, Dr. Feldman said.

"These results compare favorably to historic results and, in fact, look similar to what would be expected in IGCCCG good- or intermediate-risk patients," he added.

At the time of the analysis, 80% of patients remained progression free and only two had died, resulting in an estimated 3-year overall survival rate of 95%.

TIP had an acceptable safety profile, with no treatment-related deaths and grade 3/4 events limited to hematologic or electrolyte abnormalities, Dr. Feldman said.

Dr. Feldman reported having no financial disclosures. A coauthor reported a consultant/advisory role with Bristol-Myers Squibb.

pwendling@frontlinemedcom.com

CHICAGO – The salvage chemotherapy regimen of paclitaxel, ifosfamide, and cisplatin was active in the first-line treatment of intermediate- and poor-risk germ cell tumors in a small multicenter phase II study.

Overall, 28 of 41 evaluable patients achieved a complete response (68%), including 57% of intermediate risk (8/14) and 74% of poor-risk (20/27) patients.

"TIP demonstrated promising efficacy and met its prespecified endpoint as worthy of further study," Dr. Darren Feldman said at the annual meeting of the American Society of Clinical Oncology.

Paclitaxel (Taxol), ifosfamide (Ifex) and cisplatin (Platinol), or TIP, has become a standard regimen for germ cell tumor patients requiring salvage chemotherapy, demonstrating an approximately 70% complete response rate and 63% progression-free survival after a median of 6 years in relapsed patients.

As a result of the findings, a multicenter, randomized phase II trial has been initiated comparing TIP with standard BEP (bleomycin, etoposide, and cisplatin) as first-line therapy in intermediate- and poor-risk patients, said Dr. Feldman, with Memorial Sloan-Kettering Cancer Center in New York.

The current trial enrolled 44 men with germ cell tumors that were International Germ Cell Cancer Collaborative Group (IGCCCG) poor-risk (66%) or modified intermediate-risk, defined by serum lactate dehydrogenase (LDH) three times the upper limit of normal, if LDH was the only intermediate-risk criterion.

Histology was non-seminoma in 86% and the testis was the primary tumor site in 68%. Median patient age was 27 years.

Four cycles of TIP every 21 days was given, as planned, in 89% of patients. The regimen contained paclitaxel 120 mg/m² daily on days 1-2; ifosfamide 1,200 mg/m² mixed 1:1 with Mesna 1,200 mg/m², both daily on days 1-5; and cisplatin 20 mg/m² daily on days 1-5. Peg-filgrastim 6 mg was given subcutaneously as neutropenic fever prophylaxis on day 6 or 7.

An additional one to two cycles of adjuvant TIP could be administered if viable germ cell tumor was found at postchemotherapy surgery. Paclitaxel was initially dosed at 240 mg/m² over 5 days, but the dosing was changed to 2 days because of allergic infusion reactions.

In all, 27 of the 41 patients achieved a complete response to chemotherapy, defined by marker and radiographic normalization or marker normalization with full resection of all tumor masses and pathology revealing teratoma or necrosis, Dr. Feldman said.

One patient achieved a complete response to chemotherapy plus surgery, defined by marker normalization plus full resection with viable germ cell tumor in the specimen, but negative margins.

Partial responses, lasting 4 weeks with negative markers, were observed in 36% of intermediate-risk (5/14) and 4% of poor-risk patients (1/27). Favorable responses (CR plus PR) were seen in 93% and 78%, and incomplete responses in 7% and 22%.

After a median follow-up of 3.1 years, the estimated progression-free survival was 79% overall, 87% among intermediate-risk patients and 76% among poor-risk patients, Dr. Feldman said.

"These results compare favorably to historic results and, in fact, look similar to what would be expected in IGCCCG good- or intermediate-risk patients," he added.

At the time of the analysis, 80% of patients remained progression free and only two had died, resulting in an estimated 3-year overall survival rate of 95%.

TIP had an acceptable safety profile, with no treatment-related deaths and grade 3/4 events limited to hematologic or electrolyte abnormalities, Dr. Feldman said.

Dr. Feldman reported having no financial disclosures. A coauthor reported a consultant/advisory role with Bristol-Myers Squibb.

pwendling@frontlinemedcom.com