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Prior clopidogrel tied to more events in medically treated ACS patients
NEW YORK (Reuters Health) - Among medically treated patients with acute coronary syndrome (ACS), prior clopidogrel therapy appears to be associated with more cardiovascular events, researchers have found.
As Dr. Chee Tang Chin told Reuters Health by email, "We found that among patients who were admitted for an acute coronary syndrome and did not undergo coronary revascularization, those patients who were already taking clopidogrel were at a higher risk for a subsequent
cardiovascular event, as compared to patients not taking clopidogrel on admission."
The study, a prespecified subanalysis of the TRILOGY ACS trial, was published online March 30 in Heart.
Of almost 9,000 patients, 73% first received clopidogrel in-hospital within 72 hours of presentation and daily until randomization to clopidogrel versus prasugrel (plus aspirin). The remaining 27% were taking clopidogrel prior to admission and continued daily clopidogrel therapy until the date of randomization.
Over 30 months, those with prior clopidogrel use had a significantly higher frequency of cardiovascular death, MI and stroke (20.8% vs. 18.3%, p=0.002). There was no significant difference in the frequency of bleeding events.
Dr. Chin pointed out that in the prior users, "This excess risk was largely accounted for by the higher burden of high-risk co-morbidities among this group, such as diabetes and prior
cardiovascular disease. However, consistent with the overall TRILOGY-ACS results, the use of a more potent antiplatelet agent such as prasugrel did not modify this risk."
"These results," Dr. Chin concluded, "are important as they imply that among ACS patients treated only medically, strategies beyond platelet inhibition need to be considered for further optimizing outcomes."
NEW YORK (Reuters Health) - Among medically treated patients with acute coronary syndrome (ACS), prior clopidogrel therapy appears to be associated with more cardiovascular events, researchers have found.
As Dr. Chee Tang Chin told Reuters Health by email, "We found that among patients who were admitted for an acute coronary syndrome and did not undergo coronary revascularization, those patients who were already taking clopidogrel were at a higher risk for a subsequent
cardiovascular event, as compared to patients not taking clopidogrel on admission."
The study, a prespecified subanalysis of the TRILOGY ACS trial, was published online March 30 in Heart.
Of almost 9,000 patients, 73% first received clopidogrel in-hospital within 72 hours of presentation and daily until randomization to clopidogrel versus prasugrel (plus aspirin). The remaining 27% were taking clopidogrel prior to admission and continued daily clopidogrel therapy until the date of randomization.
Over 30 months, those with prior clopidogrel use had a significantly higher frequency of cardiovascular death, MI and stroke (20.8% vs. 18.3%, p=0.002). There was no significant difference in the frequency of bleeding events.
Dr. Chin pointed out that in the prior users, "This excess risk was largely accounted for by the higher burden of high-risk co-morbidities among this group, such as diabetes and prior
cardiovascular disease. However, consistent with the overall TRILOGY-ACS results, the use of a more potent antiplatelet agent such as prasugrel did not modify this risk."
"These results," Dr. Chin concluded, "are important as they imply that among ACS patients treated only medically, strategies beyond platelet inhibition need to be considered for further optimizing outcomes."
NEW YORK (Reuters Health) - Among medically treated patients with acute coronary syndrome (ACS), prior clopidogrel therapy appears to be associated with more cardiovascular events, researchers have found.
As Dr. Chee Tang Chin told Reuters Health by email, "We found that among patients who were admitted for an acute coronary syndrome and did not undergo coronary revascularization, those patients who were already taking clopidogrel were at a higher risk for a subsequent
cardiovascular event, as compared to patients not taking clopidogrel on admission."
The study, a prespecified subanalysis of the TRILOGY ACS trial, was published online March 30 in Heart.
Of almost 9,000 patients, 73% first received clopidogrel in-hospital within 72 hours of presentation and daily until randomization to clopidogrel versus prasugrel (plus aspirin). The remaining 27% were taking clopidogrel prior to admission and continued daily clopidogrel therapy until the date of randomization.
Over 30 months, those with prior clopidogrel use had a significantly higher frequency of cardiovascular death, MI and stroke (20.8% vs. 18.3%, p=0.002). There was no significant difference in the frequency of bleeding events.
Dr. Chin pointed out that in the prior users, "This excess risk was largely accounted for by the higher burden of high-risk co-morbidities among this group, such as diabetes and prior
cardiovascular disease. However, consistent with the overall TRILOGY-ACS results, the use of a more potent antiplatelet agent such as prasugrel did not modify this risk."
"These results," Dr. Chin concluded, "are important as they imply that among ACS patients treated only medically, strategies beyond platelet inhibition need to be considered for further optimizing outcomes."
Team designs ‘targeted EPO’
Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).
This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.
The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.
Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.
The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.
“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.
“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”
To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.
Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.
When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.
In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.
“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”
“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.
“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”
The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.” 
Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).
This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.
The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.
Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.
The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.
“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.
“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”
To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.
Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.
When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.
In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.
“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”
“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.
“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”
The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”
Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).
This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.
The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.
Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.
The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.
“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.
“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”
To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.
Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.
When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.
In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.
“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”
“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.
“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”
The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”
Childhood cancer risk linked to mother’s birthplace
Photo by Nina Matthews
New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.
The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.
However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).
Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.
The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.
The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.
To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.
For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.
When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.
For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.
For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.
The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.
These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.
Photo by Nina Matthews
New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.
The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.
However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).
Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.
The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.
The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.
To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.
For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.
When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.
For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.
For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.
The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.
These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.
Photo by Nina Matthews
New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.
The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.
However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).
Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.
The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.
The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.
To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.
For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.
When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.
For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.
For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.
The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.
These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.
High-dose MTX improves EFS in high-risk B-ALL
Photo by Bill Branson
High-dose methotrexate (MTX) is more effective than escalating doses of MTX for young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to a study published in the Journal of Clinical Oncology.
Patients who received high-dose MTX during interim maintenance 1 had significantly better event-free survival (EFS) than those who received escalating MTX.
In addition, the study showed that substituting dexamethasone for prednisone during induction was beneficial for younger—but not older—patients.
The high-dose MTX protocol outlined in this study, and the use of dexamethasone in younger patients, has become the standard practice for the treatment of high-risk ALL patients in North America.
Prior to the release of the initial study results, which were first presented last year at the ASCO Annual Meeting, the standard of care for high-risk ALL patients in North America was escalating MTX.
“One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion, by giving higher doses,” said study investigator William L. Carroll, MD, of NYU Langone Medical Center in New York, New York.
“We designed this study to compare high-dose and escalating methotrexate to determine the best way to use this drug to increase the survival of high-risk ALL patients.”
Treatment
Between January 2004 and January 2011, Dr Carroll and his colleagues enrolled 3154 patients, ages 1 to 30, with newly diagnosed, high-risk B-ALL. After exclusions, 2914 patients were randomized to treatment.
Using a 2 × 2 factorial design, the patients were randomized to receive dexamethasone for 14 days or prednisone for 28 days during induction and high-dose MTX or Capizzi escalating-dose MTX plus pegaspargase during interim maintenance 1.
So the treatment groups were as follows:
- Prednisone and escalating MTX (n=926)
- Prednisone and high-dose MTX (n=926)
- Dexamethasone and escalating MTX (n=535)
- Dexamethasone and high-dose MTX (n=527).
MTX results
At the planned interim analysis, the 5-year EFS was 82% among patients who received high-dose MTX and 75.4% among those who received escalating MTX (P=0.006).
The final data showed 5-year EFS rates of 79.6% and 75.2%, respectively (P=0.008) and 5-year overall survival rates of 88.9% and 86.1%, respectively (P=0.025).
There was a higher rate of febrile neutropenia during interim maintenance 1 among patients who received escalating MTX than among those who received high-dose MTX—8.3% and 5.1%, respectively (P=0.003).
There were 5 cases of ischemic cerebrovascular toxicity among patients who received high-dose MTX and none among the patients who received escalating MTX (P=0.03).
But there were no other significant differences in adverse events between the high-dose and escalating-dose MTX groups.
Corticosteroid results
Patients age 10 and older saw no benefit from dexamethasone, and, in fact, were at much higher risk of developing osteonecrosis. Because of this risk, the corticosteroid induction arm of this study was closed early, in 2008.
However, the investigators found that patients younger than age 10 did benefit from dexamethasone exposure.
Specifically, patients under 10 who received dexamethasone and high-dose MTX had significantly better EFS than patients who received the other 3 treatment regimens.
The 5-year EFS rate was 91.2% in the dexamethasone and high-dose MTX arm, 83.2% in the dexamethasone and escalating MTX arm, 80.8% in the prednisone and high-dose MTX arm, and 82.1% in the prednisone and escalating MTX arm (P=0.015).
For patients of all ages, there was a higher rate of febrile neutropenia during induction among patients who received dexamethasone than among those who received prednisone—18.2% and 11.0%, respectively (P<0.001).
Patients who received dexamethasone also had a higher rate of infections/infestations—29.4% and 20.3%, respectively (P<0.001).
However, there was no significant difference in induction death rate—1.9% and 1.8%, respectively (P=0.87). The same was true when the investigators looked only at patients younger than 10 (P=0.71) or at patients 10 and older (P=0.69).
Among patients ages 10 and older who participated in the induction corticosteroid randomization before it was closed, the 5-year cumulative incidence of osteonecrosis was 24.3% for patients who received dexamethasone and 15.9% for those who received prednisone (P=0.001).
There were no other significant differences in adverse events between the 2 corticosteroid regimens.
Photo by Bill Branson
High-dose methotrexate (MTX) is more effective than escalating doses of MTX for young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to a study published in the Journal of Clinical Oncology.
Patients who received high-dose MTX during interim maintenance 1 had significantly better event-free survival (EFS) than those who received escalating MTX.
In addition, the study showed that substituting dexamethasone for prednisone during induction was beneficial for younger—but not older—patients.
The high-dose MTX protocol outlined in this study, and the use of dexamethasone in younger patients, has become the standard practice for the treatment of high-risk ALL patients in North America.
Prior to the release of the initial study results, which were first presented last year at the ASCO Annual Meeting, the standard of care for high-risk ALL patients in North America was escalating MTX.
“One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion, by giving higher doses,” said study investigator William L. Carroll, MD, of NYU Langone Medical Center in New York, New York.
“We designed this study to compare high-dose and escalating methotrexate to determine the best way to use this drug to increase the survival of high-risk ALL patients.”
Treatment
Between January 2004 and January 2011, Dr Carroll and his colleagues enrolled 3154 patients, ages 1 to 30, with newly diagnosed, high-risk B-ALL. After exclusions, 2914 patients were randomized to treatment.
Using a 2 × 2 factorial design, the patients were randomized to receive dexamethasone for 14 days or prednisone for 28 days during induction and high-dose MTX or Capizzi escalating-dose MTX plus pegaspargase during interim maintenance 1.
So the treatment groups were as follows:
- Prednisone and escalating MTX (n=926)
- Prednisone and high-dose MTX (n=926)
- Dexamethasone and escalating MTX (n=535)
- Dexamethasone and high-dose MTX (n=527).
MTX results
At the planned interim analysis, the 5-year EFS was 82% among patients who received high-dose MTX and 75.4% among those who received escalating MTX (P=0.006).
The final data showed 5-year EFS rates of 79.6% and 75.2%, respectively (P=0.008) and 5-year overall survival rates of 88.9% and 86.1%, respectively (P=0.025).
There was a higher rate of febrile neutropenia during interim maintenance 1 among patients who received escalating MTX than among those who received high-dose MTX—8.3% and 5.1%, respectively (P=0.003).
There were 5 cases of ischemic cerebrovascular toxicity among patients who received high-dose MTX and none among the patients who received escalating MTX (P=0.03).
But there were no other significant differences in adverse events between the high-dose and escalating-dose MTX groups.
Corticosteroid results
Patients age 10 and older saw no benefit from dexamethasone, and, in fact, were at much higher risk of developing osteonecrosis. Because of this risk, the corticosteroid induction arm of this study was closed early, in 2008.
However, the investigators found that patients younger than age 10 did benefit from dexamethasone exposure.
Specifically, patients under 10 who received dexamethasone and high-dose MTX had significantly better EFS than patients who received the other 3 treatment regimens.
The 5-year EFS rate was 91.2% in the dexamethasone and high-dose MTX arm, 83.2% in the dexamethasone and escalating MTX arm, 80.8% in the prednisone and high-dose MTX arm, and 82.1% in the prednisone and escalating MTX arm (P=0.015).
For patients of all ages, there was a higher rate of febrile neutropenia during induction among patients who received dexamethasone than among those who received prednisone—18.2% and 11.0%, respectively (P<0.001).
Patients who received dexamethasone also had a higher rate of infections/infestations—29.4% and 20.3%, respectively (P<0.001).
However, there was no significant difference in induction death rate—1.9% and 1.8%, respectively (P=0.87). The same was true when the investigators looked only at patients younger than 10 (P=0.71) or at patients 10 and older (P=0.69).
Among patients ages 10 and older who participated in the induction corticosteroid randomization before it was closed, the 5-year cumulative incidence of osteonecrosis was 24.3% for patients who received dexamethasone and 15.9% for those who received prednisone (P=0.001).
There were no other significant differences in adverse events between the 2 corticosteroid regimens.
Photo by Bill Branson
High-dose methotrexate (MTX) is more effective than escalating doses of MTX for young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to a study published in the Journal of Clinical Oncology.
Patients who received high-dose MTX during interim maintenance 1 had significantly better event-free survival (EFS) than those who received escalating MTX.
In addition, the study showed that substituting dexamethasone for prednisone during induction was beneficial for younger—but not older—patients.
The high-dose MTX protocol outlined in this study, and the use of dexamethasone in younger patients, has become the standard practice for the treatment of high-risk ALL patients in North America.
Prior to the release of the initial study results, which were first presented last year at the ASCO Annual Meeting, the standard of care for high-risk ALL patients in North America was escalating MTX.
“One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion, by giving higher doses,” said study investigator William L. Carroll, MD, of NYU Langone Medical Center in New York, New York.
“We designed this study to compare high-dose and escalating methotrexate to determine the best way to use this drug to increase the survival of high-risk ALL patients.”
Treatment
Between January 2004 and January 2011, Dr Carroll and his colleagues enrolled 3154 patients, ages 1 to 30, with newly diagnosed, high-risk B-ALL. After exclusions, 2914 patients were randomized to treatment.
Using a 2 × 2 factorial design, the patients were randomized to receive dexamethasone for 14 days or prednisone for 28 days during induction and high-dose MTX or Capizzi escalating-dose MTX plus pegaspargase during interim maintenance 1.
So the treatment groups were as follows:
- Prednisone and escalating MTX (n=926)
- Prednisone and high-dose MTX (n=926)
- Dexamethasone and escalating MTX (n=535)
- Dexamethasone and high-dose MTX (n=527).
MTX results
At the planned interim analysis, the 5-year EFS was 82% among patients who received high-dose MTX and 75.4% among those who received escalating MTX (P=0.006).
The final data showed 5-year EFS rates of 79.6% and 75.2%, respectively (P=0.008) and 5-year overall survival rates of 88.9% and 86.1%, respectively (P=0.025).
There was a higher rate of febrile neutropenia during interim maintenance 1 among patients who received escalating MTX than among those who received high-dose MTX—8.3% and 5.1%, respectively (P=0.003).
There were 5 cases of ischemic cerebrovascular toxicity among patients who received high-dose MTX and none among the patients who received escalating MTX (P=0.03).
But there were no other significant differences in adverse events between the high-dose and escalating-dose MTX groups.
Corticosteroid results
Patients age 10 and older saw no benefit from dexamethasone, and, in fact, were at much higher risk of developing osteonecrosis. Because of this risk, the corticosteroid induction arm of this study was closed early, in 2008.
However, the investigators found that patients younger than age 10 did benefit from dexamethasone exposure.
Specifically, patients under 10 who received dexamethasone and high-dose MTX had significantly better EFS than patients who received the other 3 treatment regimens.
The 5-year EFS rate was 91.2% in the dexamethasone and high-dose MTX arm, 83.2% in the dexamethasone and escalating MTX arm, 80.8% in the prednisone and high-dose MTX arm, and 82.1% in the prednisone and escalating MTX arm (P=0.015).
For patients of all ages, there was a higher rate of febrile neutropenia during induction among patients who received dexamethasone than among those who received prednisone—18.2% and 11.0%, respectively (P<0.001).
Patients who received dexamethasone also had a higher rate of infections/infestations—29.4% and 20.3%, respectively (P<0.001).
However, there was no significant difference in induction death rate—1.9% and 1.8%, respectively (P=0.87). The same was true when the investigators looked only at patients younger than 10 (P=0.71) or at patients 10 and older (P=0.69).
Among patients ages 10 and older who participated in the induction corticosteroid randomization before it was closed, the 5-year cumulative incidence of osteonecrosis was 24.3% for patients who received dexamethasone and 15.9% for those who received prednisone (P=0.001).
There were no other significant differences in adverse events between the 2 corticosteroid regimens.
Study suggests tests overused in monoclonal gammopathies
Photo by Phil Jones
A series of tests used to diagnose and monitor monoclonal gammopathies may fail to benefit patients while increasing healthcare costs, according to research published in The American Journal of Clinical Pathology.
Researchers conducted a review of all tests for investigating monoclonal gammopathies at a single institution and found that fewer than half of the serum immunofixation and serum free light chain assays performed were actually warranted.
According to the researchers, these results suggest that, instead of ordering individual tests, physicians should request an initial workup for monoclonal gammopathy.
Once pathologists interpret results of a screening serum protein electrophoresis (SPEP) and examine the patient’s medical record, they can decide what, if any, additional tests are needed.
“These are stepwise things,” said study author Gurmukh Singh, MD, PhD, of the Medical College of Georgia at Augusta University.
“If it’s a new patient, do this. If it’s a known patient, do that. Results drive it. That will reduce the number of tests that are done without in any way being of detriment to the patient or the quality of care.”
To conduct this study, Dr Singh and his colleagues reviewed the history of 237 patients, ages 19 to 87, who had a total of 1503 episodes of testing.
In addition to SPEP, many patients had serum immunofixation electrophoresis and/or serum free light chain assays.
But the researchers found that only 46% of the serum immunofixation and 42% of the serum free light chain assays were warranted.
The 2 tests were ordered multiple times in patients in whom M-protein was easily detected with SPEP. In fact, for most patients with measurable levels of M-protein, SPEP can be used to follow the course of the disease and treatment, the researchers said.
“About 40% to 50% of the second tests are not needed or adding value,” Dr Sing stressed.
In fact, he and his colleagues estimated that putting an end to unnecessary testing would have saved $64,182.95 per year in healthcare costs at this institution.
Therefore, the researchers propose using an algorithm that would put more of the decision-making in the hands of pathologists interpreting the tests.
An example of when serum immunofixation and serum free light chain assays should be done at least once is in a new patient when M-protein is first found, Dr Singh said. The additional tests might also be beneficial for patients under treatment for multiple myeloma, to ensure there are no trace amounts left of the abnormal protein.
Dr Singh added that testing patterns similar to those observed in this study are in play in hospitals across the US. However, a protocol similar to the one he is proposing has safely enabled up to a 60% reduction in the volume of second tests at a Missouri hospital where it has been in use for about 8 years.
“It’s better for patients and for healthcare delivery in general,” Dr Singh said. “Why spend money that you don’t need to spend when you are not gaining information that will benefit the patient’s outcome?”
Photo by Phil Jones
A series of tests used to diagnose and monitor monoclonal gammopathies may fail to benefit patients while increasing healthcare costs, according to research published in The American Journal of Clinical Pathology.
Researchers conducted a review of all tests for investigating monoclonal gammopathies at a single institution and found that fewer than half of the serum immunofixation and serum free light chain assays performed were actually warranted.
According to the researchers, these results suggest that, instead of ordering individual tests, physicians should request an initial workup for monoclonal gammopathy.
Once pathologists interpret results of a screening serum protein electrophoresis (SPEP) and examine the patient’s medical record, they can decide what, if any, additional tests are needed.
“These are stepwise things,” said study author Gurmukh Singh, MD, PhD, of the Medical College of Georgia at Augusta University.
“If it’s a new patient, do this. If it’s a known patient, do that. Results drive it. That will reduce the number of tests that are done without in any way being of detriment to the patient or the quality of care.”
To conduct this study, Dr Singh and his colleagues reviewed the history of 237 patients, ages 19 to 87, who had a total of 1503 episodes of testing.
In addition to SPEP, many patients had serum immunofixation electrophoresis and/or serum free light chain assays.
But the researchers found that only 46% of the serum immunofixation and 42% of the serum free light chain assays were warranted.
The 2 tests were ordered multiple times in patients in whom M-protein was easily detected with SPEP. In fact, for most patients with measurable levels of M-protein, SPEP can be used to follow the course of the disease and treatment, the researchers said.
“About 40% to 50% of the second tests are not needed or adding value,” Dr Sing stressed.
In fact, he and his colleagues estimated that putting an end to unnecessary testing would have saved $64,182.95 per year in healthcare costs at this institution.
Therefore, the researchers propose using an algorithm that would put more of the decision-making in the hands of pathologists interpreting the tests.
An example of when serum immunofixation and serum free light chain assays should be done at least once is in a new patient when M-protein is first found, Dr Singh said. The additional tests might also be beneficial for patients under treatment for multiple myeloma, to ensure there are no trace amounts left of the abnormal protein.
Dr Singh added that testing patterns similar to those observed in this study are in play in hospitals across the US. However, a protocol similar to the one he is proposing has safely enabled up to a 60% reduction in the volume of second tests at a Missouri hospital where it has been in use for about 8 years.
“It’s better for patients and for healthcare delivery in general,” Dr Singh said. “Why spend money that you don’t need to spend when you are not gaining information that will benefit the patient’s outcome?”
Photo by Phil Jones
A series of tests used to diagnose and monitor monoclonal gammopathies may fail to benefit patients while increasing healthcare costs, according to research published in The American Journal of Clinical Pathology.
Researchers conducted a review of all tests for investigating monoclonal gammopathies at a single institution and found that fewer than half of the serum immunofixation and serum free light chain assays performed were actually warranted.
According to the researchers, these results suggest that, instead of ordering individual tests, physicians should request an initial workup for monoclonal gammopathy.
Once pathologists interpret results of a screening serum protein electrophoresis (SPEP) and examine the patient’s medical record, they can decide what, if any, additional tests are needed.
“These are stepwise things,” said study author Gurmukh Singh, MD, PhD, of the Medical College of Georgia at Augusta University.
“If it’s a new patient, do this. If it’s a known patient, do that. Results drive it. That will reduce the number of tests that are done without in any way being of detriment to the patient or the quality of care.”
To conduct this study, Dr Singh and his colleagues reviewed the history of 237 patients, ages 19 to 87, who had a total of 1503 episodes of testing.
In addition to SPEP, many patients had serum immunofixation electrophoresis and/or serum free light chain assays.
But the researchers found that only 46% of the serum immunofixation and 42% of the serum free light chain assays were warranted.
The 2 tests were ordered multiple times in patients in whom M-protein was easily detected with SPEP. In fact, for most patients with measurable levels of M-protein, SPEP can be used to follow the course of the disease and treatment, the researchers said.
“About 40% to 50% of the second tests are not needed or adding value,” Dr Sing stressed.
In fact, he and his colleagues estimated that putting an end to unnecessary testing would have saved $64,182.95 per year in healthcare costs at this institution.
Therefore, the researchers propose using an algorithm that would put more of the decision-making in the hands of pathologists interpreting the tests.
An example of when serum immunofixation and serum free light chain assays should be done at least once is in a new patient when M-protein is first found, Dr Singh said. The additional tests might also be beneficial for patients under treatment for multiple myeloma, to ensure there are no trace amounts left of the abnormal protein.
Dr Singh added that testing patterns similar to those observed in this study are in play in hospitals across the US. However, a protocol similar to the one he is proposing has safely enabled up to a 60% reduction in the volume of second tests at a Missouri hospital where it has been in use for about 8 years.
“It’s better for patients and for healthcare delivery in general,” Dr Singh said. “Why spend money that you don’t need to spend when you are not gaining information that will benefit the patient’s outcome?”
An unusual case of non-small-cell lung cancer presenting as spontaneous cardiac tamponade
Hemorrhagic pericardial effusion with associated cardiac tamponade as a de novo sign of malignancy is seen in about 2% of patients.1 Consequently, cardiac tamponade is an oncologic emergency and considered a unique presentation of a malignancy.2 Cancer emergency is defined as an acute condition that is caused directly by the cancer itself or its treatment and requires intervention to avoid death or significant morbidity.3 The mechanism by which cardiac tamponade is classified as a life-threatening emergency stems from its impairment of right ventricular filling, resulting in ventricular diastolic collapse and decreased cardiac output, which can ultimately lead to death.4
Click on the PDF icon at the top of this introduction to read the full article.
Hemorrhagic pericardial effusion with associated cardiac tamponade as a de novo sign of malignancy is seen in about 2% of patients.1 Consequently, cardiac tamponade is an oncologic emergency and considered a unique presentation of a malignancy.2 Cancer emergency is defined as an acute condition that is caused directly by the cancer itself or its treatment and requires intervention to avoid death or significant morbidity.3 The mechanism by which cardiac tamponade is classified as a life-threatening emergency stems from its impairment of right ventricular filling, resulting in ventricular diastolic collapse and decreased cardiac output, which can ultimately lead to death.4
Click on the PDF icon at the top of this introduction to read the full article.
Hemorrhagic pericardial effusion with associated cardiac tamponade as a de novo sign of malignancy is seen in about 2% of patients.1 Consequently, cardiac tamponade is an oncologic emergency and considered a unique presentation of a malignancy.2 Cancer emergency is defined as an acute condition that is caused directly by the cancer itself or its treatment and requires intervention to avoid death or significant morbidity.3 The mechanism by which cardiac tamponade is classified as a life-threatening emergency stems from its impairment of right ventricular filling, resulting in ventricular diastolic collapse and decreased cardiac output, which can ultimately lead to death.4
Click on the PDF icon at the top of this introduction to read the full article.
Reaching high-risk underserved individuals for cancer genetic counseling by video-teleconferencing
Background Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes.
Objective To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region.
Methods Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment.
Results The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community.
Limitations Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling.
Conclusion Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population.
Funding Supported primarily by a grant from the Cancer Prevention and Research Institute of Texas (PP120089 [GT]), NIH-NCI P30 CA54174 (CTRC at UTHSCSA); and a grant from the Valley Baptist Legacy Foundation.
Click on the PDF icon at the top of this introduction to read the full article.
Background Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes.
Objective To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region.
Methods Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment.
Results The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community.
Limitations Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling.
Conclusion Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population.
Funding Supported primarily by a grant from the Cancer Prevention and Research Institute of Texas (PP120089 [GT]), NIH-NCI P30 CA54174 (CTRC at UTHSCSA); and a grant from the Valley Baptist Legacy Foundation.
Click on the PDF icon at the top of this introduction to read the full article.
Background Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes.
Objective To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region.
Methods Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment.
Results The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community.
Limitations Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling.
Conclusion Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population.
Funding Supported primarily by a grant from the Cancer Prevention and Research Institute of Texas (PP120089 [GT]), NIH-NCI P30 CA54174 (CTRC at UTHSCSA); and a grant from the Valley Baptist Legacy Foundation.
Click on the PDF icon at the top of this introduction to read the full article.
Diagnostic work-up for the detection of malnutrition in hospitalized cancer patients
Objective To evaluate and compare the use of various diagnostic tests for the detection of malnutrition in patients hospitalized for cancer treatment.
Methods In this single-center, non-interventional reliability study, the nutritional status of 50 patients with cancer was assessed using the Nutritional Risk Screening (NRS-2002), a bioimpedance analysis (BIA), and the measurement of laboratory parameters that reflect the serum visceral protein level. For statistical analysis, the comparison of means and the agreement of the methods were calculated.
Results NRS-2002, BIA, and lab parameters differed widely among patients classified as well-nourished or malnourished (10%- 80%, depending on the method). Significant results in the comparison of means were observed for body mass index, serum protein, and some BIA parameters. The analysis of agreement identified a compelling agreement for pre-albumin and retinol-binding protein (RBP) (kappa = 0.81).
Limitations Small sample size, heterogeneous group of patients, non-interventional reliability study.
Conclusion The tested diagnostic methods for detecting malnutrition did not have an evident agreement among each other with a limited exchangeability. In routine hospital practice several methods should be applied in order to identify cancer patients at risk of malnutrition.
Funding/sponsorship Fresenius Kabi provided the BIA-unit and software.
Click on the PDF icon at the top of this introduction to read the full article.
Objective To evaluate and compare the use of various diagnostic tests for the detection of malnutrition in patients hospitalized for cancer treatment.
Methods In this single-center, non-interventional reliability study, the nutritional status of 50 patients with cancer was assessed using the Nutritional Risk Screening (NRS-2002), a bioimpedance analysis (BIA), and the measurement of laboratory parameters that reflect the serum visceral protein level. For statistical analysis, the comparison of means and the agreement of the methods were calculated.
Results NRS-2002, BIA, and lab parameters differed widely among patients classified as well-nourished or malnourished (10%- 80%, depending on the method). Significant results in the comparison of means were observed for body mass index, serum protein, and some BIA parameters. The analysis of agreement identified a compelling agreement for pre-albumin and retinol-binding protein (RBP) (kappa = 0.81).
Limitations Small sample size, heterogeneous group of patients, non-interventional reliability study.
Conclusion The tested diagnostic methods for detecting malnutrition did not have an evident agreement among each other with a limited exchangeability. In routine hospital practice several methods should be applied in order to identify cancer patients at risk of malnutrition.
Funding/sponsorship Fresenius Kabi provided the BIA-unit and software.
Click on the PDF icon at the top of this introduction to read the full article.
Objective To evaluate and compare the use of various diagnostic tests for the detection of malnutrition in patients hospitalized for cancer treatment.
Methods In this single-center, non-interventional reliability study, the nutritional status of 50 patients with cancer was assessed using the Nutritional Risk Screening (NRS-2002), a bioimpedance analysis (BIA), and the measurement of laboratory parameters that reflect the serum visceral protein level. For statistical analysis, the comparison of means and the agreement of the methods were calculated.
Results NRS-2002, BIA, and lab parameters differed widely among patients classified as well-nourished or malnourished (10%- 80%, depending on the method). Significant results in the comparison of means were observed for body mass index, serum protein, and some BIA parameters. The analysis of agreement identified a compelling agreement for pre-albumin and retinol-binding protein (RBP) (kappa = 0.81).
Limitations Small sample size, heterogeneous group of patients, non-interventional reliability study.
Conclusion The tested diagnostic methods for detecting malnutrition did not have an evident agreement among each other with a limited exchangeability. In routine hospital practice several methods should be applied in order to identify cancer patients at risk of malnutrition.
Funding/sponsorship Fresenius Kabi provided the BIA-unit and software.
Click on the PDF icon at the top of this introduction to read the full article.
Repeated measures analysis of patient-reported outcomes in prostate cancer after abiraterone acetate
Background Metastatic castration-resistant prostate cancer (mCRPC) is typically associated with declining health-related quality of life (HR-QoL).
Objective To assess patient experience with abiraterone acetate (hereafter abiraterone) plus prednisone longitudinally.
Methods COU-AA-302 was a phase 3, multinational, randomized, double-blind study that enrolled asymptomatic or mildly symptomatic, chemotherapy-naïve patients with mCRPC. Patients were randomized to 1 g abiraterone daily plus 5 mg prednisone BID (n = 546) or placebo plus prednisone (n = 542) in continuous 28-day cycles. Patient-reported outcomes (PROs) were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, consisting of 4 well-being subscales (physical, social/family, emotional, functional) and a prostate cancer-specific subscale (PCS). The trial outcome index (TOI) is a composite of the physical well-being, functional well-being, and PCS scores. Least squares mean change from baseline at each cycle up to 1 year (cycle13) was compared between treatment arms using a mixed-effects model for repeated measures, which assumed that data were “missing at random.” A pattern-mixture model (PMM) with multiple imputation was performed to address the assumption that data were “missing not at random.”
Results Significant differences favoring abiraterone-prednisone were observed for FACT-P total, TOI, and PCS scores, and for all well-being subscales except social/family well-being over the first year of treatment. These results were supported by the PMM with multiple imputation.
Limitations Attrition after 1 year limited our ability to analyze the PRO data beyond that time point.
Conclusions Abiraterone-prednisone confers sustained HR-QoL benefits over the course of treatment.
Funding Janssen Research & Development
Click on the PDF icon at the top of this introduction to read the full article.
Background Metastatic castration-resistant prostate cancer (mCRPC) is typically associated with declining health-related quality of life (HR-QoL).
Objective To assess patient experience with abiraterone acetate (hereafter abiraterone) plus prednisone longitudinally.
Methods COU-AA-302 was a phase 3, multinational, randomized, double-blind study that enrolled asymptomatic or mildly symptomatic, chemotherapy-naïve patients with mCRPC. Patients were randomized to 1 g abiraterone daily plus 5 mg prednisone BID (n = 546) or placebo plus prednisone (n = 542) in continuous 28-day cycles. Patient-reported outcomes (PROs) were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, consisting of 4 well-being subscales (physical, social/family, emotional, functional) and a prostate cancer-specific subscale (PCS). The trial outcome index (TOI) is a composite of the physical well-being, functional well-being, and PCS scores. Least squares mean change from baseline at each cycle up to 1 year (cycle13) was compared between treatment arms using a mixed-effects model for repeated measures, which assumed that data were “missing at random.” A pattern-mixture model (PMM) with multiple imputation was performed to address the assumption that data were “missing not at random.”
Results Significant differences favoring abiraterone-prednisone were observed for FACT-P total, TOI, and PCS scores, and for all well-being subscales except social/family well-being over the first year of treatment. These results were supported by the PMM with multiple imputation.
Limitations Attrition after 1 year limited our ability to analyze the PRO data beyond that time point.
Conclusions Abiraterone-prednisone confers sustained HR-QoL benefits over the course of treatment.
Funding Janssen Research & Development
Click on the PDF icon at the top of this introduction to read the full article.
Background Metastatic castration-resistant prostate cancer (mCRPC) is typically associated with declining health-related quality of life (HR-QoL).
Objective To assess patient experience with abiraterone acetate (hereafter abiraterone) plus prednisone longitudinally.
Methods COU-AA-302 was a phase 3, multinational, randomized, double-blind study that enrolled asymptomatic or mildly symptomatic, chemotherapy-naïve patients with mCRPC. Patients were randomized to 1 g abiraterone daily plus 5 mg prednisone BID (n = 546) or placebo plus prednisone (n = 542) in continuous 28-day cycles. Patient-reported outcomes (PROs) were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, consisting of 4 well-being subscales (physical, social/family, emotional, functional) and a prostate cancer-specific subscale (PCS). The trial outcome index (TOI) is a composite of the physical well-being, functional well-being, and PCS scores. Least squares mean change from baseline at each cycle up to 1 year (cycle13) was compared between treatment arms using a mixed-effects model for repeated measures, which assumed that data were “missing at random.” A pattern-mixture model (PMM) with multiple imputation was performed to address the assumption that data were “missing not at random.”
Results Significant differences favoring abiraterone-prednisone were observed for FACT-P total, TOI, and PCS scores, and for all well-being subscales except social/family well-being over the first year of treatment. These results were supported by the PMM with multiple imputation.
Limitations Attrition after 1 year limited our ability to analyze the PRO data beyond that time point.
Conclusions Abiraterone-prednisone confers sustained HR-QoL benefits over the course of treatment.
Funding Janssen Research & Development
Click on the PDF icon at the top of this introduction to read the full article.
Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting
Background Concurrent chemotherapy radiation therapy may result in significant nausea and vomiting. There have been few studies reporting effective interventions for preventing treatment-related nausea and vomiting.
Objective To compare olanzapine with fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiotherapy for locally advanced head and neck or esophageal cancer.
Methods 120 chemotherapy and radiotherapy naïve patients with head and neck cancer who were receiving concurrent local radiation and cisplatin were randomized to receive either olanzapine or fosaprepitant in combination with palonosetron and dexamethasone for the prevention of chemotherapy- and radiation-induced nausea and vomiting. The olanzapine, palonosetron, dexamethasone (OPD) regimen was 10 mg oral olanzapine , 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 10 mg/day of oral olanzapine before chemotherapy on days 2-4. The fosaprepitant, palonosetron, dexamethasone (FPD) regimen was 150 mg IV fosaprepitant, 0.25 mg IV palonosetron, and 12 mg IV dexamethasone before chemotherapy on day 1, and 4 mg dexamethasone PO BID, before chemotherapy days 2 and 3.
Results 101 of the 120 patients were evaluable. In 51 patients who received the OPD regimen, the complete response (CR; no emesis, no rescue medication) rate was 88% for the acute period (24 h after chemotherapy), 76% for the delayed period (days 2-5), and 76% for the overall period (0-120 h). In 50 patients who received the FPD regimen, the CR was 84% acute, 74% delayed, and 74% overall (P > .01 for all periods). Patients with no nausea (0, on a scale 0-10, visual analogue scale) were: OPD: 86% acute, 71% delayed, 71% overall; FPD: 78% acute, 40% delayed, 40% overall (P > .01 for acute; P < .01 for delayed and overall) There were no grade 3 or 4 toxicities.
Conclusions CR was similar for OPD and FPD; nausea in the delayed and overall periods was signifcantly improved with OPD compared with FPD (P < .01).
Funding Reich Endowment for the Care of the Whole Patient
Click on the PDF icon at the top of this introduction to read the full article.
Background Concurrent chemotherapy radiation therapy may result in significant nausea and vomiting. There have been few studies reporting effective interventions for preventing treatment-related nausea and vomiting.
Objective To compare olanzapine with fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiotherapy for locally advanced head and neck or esophageal cancer.
Methods 120 chemotherapy and radiotherapy naïve patients with head and neck cancer who were receiving concurrent local radiation and cisplatin were randomized to receive either olanzapine or fosaprepitant in combination with palonosetron and dexamethasone for the prevention of chemotherapy- and radiation-induced nausea and vomiting. The olanzapine, palonosetron, dexamethasone (OPD) regimen was 10 mg oral olanzapine , 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 10 mg/day of oral olanzapine before chemotherapy on days 2-4. The fosaprepitant, palonosetron, dexamethasone (FPD) regimen was 150 mg IV fosaprepitant, 0.25 mg IV palonosetron, and 12 mg IV dexamethasone before chemotherapy on day 1, and 4 mg dexamethasone PO BID, before chemotherapy days 2 and 3.
Results 101 of the 120 patients were evaluable. In 51 patients who received the OPD regimen, the complete response (CR; no emesis, no rescue medication) rate was 88% for the acute period (24 h after chemotherapy), 76% for the delayed period (days 2-5), and 76% for the overall period (0-120 h). In 50 patients who received the FPD regimen, the CR was 84% acute, 74% delayed, and 74% overall (P > .01 for all periods). Patients with no nausea (0, on a scale 0-10, visual analogue scale) were: OPD: 86% acute, 71% delayed, 71% overall; FPD: 78% acute, 40% delayed, 40% overall (P > .01 for acute; P < .01 for delayed and overall) There were no grade 3 or 4 toxicities.
Conclusions CR was similar for OPD and FPD; nausea in the delayed and overall periods was signifcantly improved with OPD compared with FPD (P < .01).
Funding Reich Endowment for the Care of the Whole Patient
Click on the PDF icon at the top of this introduction to read the full article.
Background Concurrent chemotherapy radiation therapy may result in significant nausea and vomiting. There have been few studies reporting effective interventions for preventing treatment-related nausea and vomiting.
Objective To compare olanzapine with fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiotherapy for locally advanced head and neck or esophageal cancer.
Methods 120 chemotherapy and radiotherapy naïve patients with head and neck cancer who were receiving concurrent local radiation and cisplatin were randomized to receive either olanzapine or fosaprepitant in combination with palonosetron and dexamethasone for the prevention of chemotherapy- and radiation-induced nausea and vomiting. The olanzapine, palonosetron, dexamethasone (OPD) regimen was 10 mg oral olanzapine , 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 10 mg/day of oral olanzapine before chemotherapy on days 2-4. The fosaprepitant, palonosetron, dexamethasone (FPD) regimen was 150 mg IV fosaprepitant, 0.25 mg IV palonosetron, and 12 mg IV dexamethasone before chemotherapy on day 1, and 4 mg dexamethasone PO BID, before chemotherapy days 2 and 3.
Results 101 of the 120 patients were evaluable. In 51 patients who received the OPD regimen, the complete response (CR; no emesis, no rescue medication) rate was 88% for the acute period (24 h after chemotherapy), 76% for the delayed period (days 2-5), and 76% for the overall period (0-120 h). In 50 patients who received the FPD regimen, the CR was 84% acute, 74% delayed, and 74% overall (P > .01 for all periods). Patients with no nausea (0, on a scale 0-10, visual analogue scale) were: OPD: 86% acute, 71% delayed, 71% overall; FPD: 78% acute, 40% delayed, 40% overall (P > .01 for acute; P < .01 for delayed and overall) There were no grade 3 or 4 toxicities.
Conclusions CR was similar for OPD and FPD; nausea in the delayed and overall periods was signifcantly improved with OPD compared with FPD (P < .01).
Funding Reich Endowment for the Care of the Whole Patient
Click on the PDF icon at the top of this introduction to read the full article.