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Management of Bleeding Complications in Patients with Cancer
Patients with cancer can have many hematologic complications. One of the most serious is bleeding, which can range in severity from laboratory abnormalities to life-threatening hemorrhage. The bleeding can be due to complications of the cancer, its therapy, or treatment for complications of cancer such as thrombosis. This manual discusses an approach to the cancer patient with bleeding, with a specific focus on issues such as coagulation defects, thrombocytopenia, and platelet dysfunction. Bleeding complications of specific cancers and their treatment will be discussed as well.
To read the full article in PDF:
Patients with cancer can have many hematologic complications. One of the most serious is bleeding, which can range in severity from laboratory abnormalities to life-threatening hemorrhage. The bleeding can be due to complications of the cancer, its therapy, or treatment for complications of cancer such as thrombosis. This manual discusses an approach to the cancer patient with bleeding, with a specific focus on issues such as coagulation defects, thrombocytopenia, and platelet dysfunction. Bleeding complications of specific cancers and their treatment will be discussed as well.
To read the full article in PDF:
Patients with cancer can have many hematologic complications. One of the most serious is bleeding, which can range in severity from laboratory abnormalities to life-threatening hemorrhage. The bleeding can be due to complications of the cancer, its therapy, or treatment for complications of cancer such as thrombosis. This manual discusses an approach to the cancer patient with bleeding, with a specific focus on issues such as coagulation defects, thrombocytopenia, and platelet dysfunction. Bleeding complications of specific cancers and their treatment will be discussed as well.
To read the full article in PDF:
FDA approves extended-release hydrocodone with abuse-deterrent features
An extended-release formulation of hydrocodone with properties that are “expected to reduce, but not totally prevent” abuse has been approved, the Food and Drug Administration announced on Nov. 20.
The hydrocodone-only product is indicated for treating pain “severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate,” according to the FDA statement. It is not approved for as-needed pain relief, and because of its risks for abuse, misuse, and addiction, “should only be prescribed to people for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient pain management,” the FDA statement said.
The product will be marketed as Hysingla ER, by Purdue Pharma, the manufacturer of extended-release oxycodone marketed as OxyContin.
Hysingla ER comes in 20-mg, 30-mg, 40-mg, 60-mg , 100-mg, and 120-mg strengths, taken once a day; daily doses of 80 mg or more should not be prescribed to people who have not previously been treated with an opioid. These amounts are higher than immediate-release hydrocodone combination products, but the range is “comparable” to currently available extended-release opioids, the statement points out.
The tablet has properties that make it difficult to crush, break, or dissolve. It also forms a thick gel when put in liquid, which “resists passage through a hypodermic needle,” according to the prescribing information. While the product’s physical and chemical properties are expected to make abuse by these routes difficult, abuse by these routes is still possible, the FDA statement said.
As part of the FDA’s Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting opioids, Purdue is required to provide health care professionals with information on how to safely prescribe the drug and to provide documents to patients, including a medication guide with each prescription, about how to safely use, store, and dispose of these products.
The company is also required to conduct postmarketing studies to evaluate the impact of the abuse-deterrent properties on the risk of abuse and the impact of that abuse in the community, according to the statement.
“While the science of abuse deterrence is still evolving, the development of opioids that are harder to abuse is helpful in addressing the public health crisis of prescription drug abuse in the U.S.,” Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said in the statement. “Encouraging the development of opioids with abuse-deterrent properties is just one component of a broader approach to reducing abuse and misuse and will better enable the agency to balance addressing this problem with ensuring that patients have access to appropriate treatments for pain,” she added.
In October, hydrocodone was switched from a schedule III to the stricter schedule II category.
Hysingla ER is expected to be available in early 2015, according to a statement by Purdue.
In August 2014, hydrocodone was switched from a schedule III to a schedule II controlled substance.
The prescribing information is available at http://www.purduepharma.com/wp-content/uploads/hysinglaerpi.pdf.
An extended-release formulation of hydrocodone with properties that are “expected to reduce, but not totally prevent” abuse has been approved, the Food and Drug Administration announced on Nov. 20.
The hydrocodone-only product is indicated for treating pain “severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate,” according to the FDA statement. It is not approved for as-needed pain relief, and because of its risks for abuse, misuse, and addiction, “should only be prescribed to people for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient pain management,” the FDA statement said.
The product will be marketed as Hysingla ER, by Purdue Pharma, the manufacturer of extended-release oxycodone marketed as OxyContin.
Hysingla ER comes in 20-mg, 30-mg, 40-mg, 60-mg , 100-mg, and 120-mg strengths, taken once a day; daily doses of 80 mg or more should not be prescribed to people who have not previously been treated with an opioid. These amounts are higher than immediate-release hydrocodone combination products, but the range is “comparable” to currently available extended-release opioids, the statement points out.
The tablet has properties that make it difficult to crush, break, or dissolve. It also forms a thick gel when put in liquid, which “resists passage through a hypodermic needle,” according to the prescribing information. While the product’s physical and chemical properties are expected to make abuse by these routes difficult, abuse by these routes is still possible, the FDA statement said.
As part of the FDA’s Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting opioids, Purdue is required to provide health care professionals with information on how to safely prescribe the drug and to provide documents to patients, including a medication guide with each prescription, about how to safely use, store, and dispose of these products.
The company is also required to conduct postmarketing studies to evaluate the impact of the abuse-deterrent properties on the risk of abuse and the impact of that abuse in the community, according to the statement.
“While the science of abuse deterrence is still evolving, the development of opioids that are harder to abuse is helpful in addressing the public health crisis of prescription drug abuse in the U.S.,” Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said in the statement. “Encouraging the development of opioids with abuse-deterrent properties is just one component of a broader approach to reducing abuse and misuse and will better enable the agency to balance addressing this problem with ensuring that patients have access to appropriate treatments for pain,” she added.
In October, hydrocodone was switched from a schedule III to the stricter schedule II category.
Hysingla ER is expected to be available in early 2015, according to a statement by Purdue.
In August 2014, hydrocodone was switched from a schedule III to a schedule II controlled substance.
The prescribing information is available at http://www.purduepharma.com/wp-content/uploads/hysinglaerpi.pdf.
An extended-release formulation of hydrocodone with properties that are “expected to reduce, but not totally prevent” abuse has been approved, the Food and Drug Administration announced on Nov. 20.
The hydrocodone-only product is indicated for treating pain “severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate,” according to the FDA statement. It is not approved for as-needed pain relief, and because of its risks for abuse, misuse, and addiction, “should only be prescribed to people for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient pain management,” the FDA statement said.
The product will be marketed as Hysingla ER, by Purdue Pharma, the manufacturer of extended-release oxycodone marketed as OxyContin.
Hysingla ER comes in 20-mg, 30-mg, 40-mg, 60-mg , 100-mg, and 120-mg strengths, taken once a day; daily doses of 80 mg or more should not be prescribed to people who have not previously been treated with an opioid. These amounts are higher than immediate-release hydrocodone combination products, but the range is “comparable” to currently available extended-release opioids, the statement points out.
The tablet has properties that make it difficult to crush, break, or dissolve. It also forms a thick gel when put in liquid, which “resists passage through a hypodermic needle,” according to the prescribing information. While the product’s physical and chemical properties are expected to make abuse by these routes difficult, abuse by these routes is still possible, the FDA statement said.
As part of the FDA’s Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting opioids, Purdue is required to provide health care professionals with information on how to safely prescribe the drug and to provide documents to patients, including a medication guide with each prescription, about how to safely use, store, and dispose of these products.
The company is also required to conduct postmarketing studies to evaluate the impact of the abuse-deterrent properties on the risk of abuse and the impact of that abuse in the community, according to the statement.
“While the science of abuse deterrence is still evolving, the development of opioids that are harder to abuse is helpful in addressing the public health crisis of prescription drug abuse in the U.S.,” Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said in the statement. “Encouraging the development of opioids with abuse-deterrent properties is just one component of a broader approach to reducing abuse and misuse and will better enable the agency to balance addressing this problem with ensuring that patients have access to appropriate treatments for pain,” she added.
In October, hydrocodone was switched from a schedule III to the stricter schedule II category.
Hysingla ER is expected to be available in early 2015, according to a statement by Purdue.
In August 2014, hydrocodone was switched from a schedule III to a schedule II controlled substance.
The prescribing information is available at http://www.purduepharma.com/wp-content/uploads/hysinglaerpi.pdf.
FROM THE FDA
Medicare beneficiaries in hospice care get better care, have fewer costs
Medicare fee-for-service beneficiaries suffering from poor-prognosis cancer who received hospice care were found to have lower rates of hospitalizations, admissions to intensive care units, and invasive procedures than those who did not receive hospice care, according to a study published in JAMA.
“Our findings highlight the potential importance of frank discussions between physicians and patients about the realities of care at the end of life, an issue of particular importance as the Medicare administration weighs decisions around reimbursing physicians for advance care planning,” said Dr. Ziad Obermeyer of the emergency medicine department at Brigham and Women’s Hospital in Boston, and his associates.
In a matched cohort study, Dr. Obermeyer and his colleagues examined the records of 86,851 patients with poor-prognosis cancer – such as brain, pancreatic, and metastatic malignancies – using a nationally representative, 20% sample of Medicare fee-for-service beneficiaries who died in 2011. Of that group, 51,924 individuals (60%) entered hospice care prior to death, with the median time from first diagnosis to death being 13 months (JAMA 2014;312:1888-96).
The researchers then matched patients in hospice vs. nonhospice care, using factors such as age, sex, region, time from first diagnosis to death, and baseline care utilization. Each sample group consisted of 18,165 individuals, with the non–hospice-care group acting as the control. The median hospice duration for the hospice group was 11 days.
Dr. Obermeyer and his associates discovered that hospice beneficiaries had significantly lower rates of hospitalization (42%), intensive care unit admission (15%), invasive procedures (27%), and deaths in hospitals or nursing facilities (14%), compared with their nonhospice counterparts, who had a 65% rate of hospitalization, a 36% rate of intensive care unit admission, a 51% rate of invasive procedures, and a 74% rate of deaths in hospitals or nursing facilities.
Furthermore, the authors found that nonhospice beneficiaries had a higher rate of health care utilization, largely for acute conditions that were not directly related to their cancer, and higher overall costs. On average, costs for hospice beneficiaries were $62,819, while costs for nonhospice beneficiaries were $71,517.
“Hospice enrollment of 5 to 8 weeks produced the greatest savings; shorter stays produced fewer savings, likely because of both hospice initiation costs, and need for intensive symptom palliation in the days before death,” Dr. Obermeyer and his coauthors wrote. “Cost trajectories began to diverge in the week after hospice enrollment, implying that baseline differences between hospice and nonhospice beneficiaries were not responsible for cost differences,” they added.
The study was supported by grants from the National Institutes of Health, the National Cancer Institute, and the Agency for Healthcare Research and Quality. The authors reported no relevant conflicts of interest.
Although the study by Obermeyer et al. adds to the evidence regarding hospice care for patients with poor-prognosis cancer, several caveats should be considered. An important threat to the validity of this study was that the unobserved difference in preferences for aggressive care may explain the observed cost savings. Rightfully, the authors acknowledge this and other limitations, such as restriction of the study population to patients with cancer, exclusion of Medicare beneficiaries with managed care and non-Medicare patients, and reliance only on claims-based information for risk adjustments, Dr. Joan M. Teno and Pedro L. Gozalo, Ph.D., both of the Brown University School of Public Health, Providence, R.I., wrote in an editorial accompanying the study.
The findings from this study raise several important policy issues, they said. If hospice saves money, should health care policy promote increased hospice access? Perhaps an even larger policy issue involves the role of costs and not quality in driving U.S. health policy in care of the seriously ill and those at the close of life (JAMA 2014;312:1868-69).
The pressing policy issue in the United States involves not only patients dying of poor-prognosis cancers, but patients with noncancer chronic illness for whom the costs of prolonged hospice stays exceed the potential savings from hospitalizations. Even in that policy debate, focusing solely on expenditures is not warranted. That hospice or hospital-based palliative care teams save money is ethically defensible only if there is improvement in the quality of care and medical decisions are consistent with the informed patient’s wishes and goals of care.
Dr. Teno is a professor at the Brown University School of Public Health. Dr. Gozalo is an associate professor at the university.
Although the study by Obermeyer et al. adds to the evidence regarding hospice care for patients with poor-prognosis cancer, several caveats should be considered. An important threat to the validity of this study was that the unobserved difference in preferences for aggressive care may explain the observed cost savings. Rightfully, the authors acknowledge this and other limitations, such as restriction of the study population to patients with cancer, exclusion of Medicare beneficiaries with managed care and non-Medicare patients, and reliance only on claims-based information for risk adjustments, Dr. Joan M. Teno and Pedro L. Gozalo, Ph.D., both of the Brown University School of Public Health, Providence, R.I., wrote in an editorial accompanying the study.
The findings from this study raise several important policy issues, they said. If hospice saves money, should health care policy promote increased hospice access? Perhaps an even larger policy issue involves the role of costs and not quality in driving U.S. health policy in care of the seriously ill and those at the close of life (JAMA 2014;312:1868-69).
The pressing policy issue in the United States involves not only patients dying of poor-prognosis cancers, but patients with noncancer chronic illness for whom the costs of prolonged hospice stays exceed the potential savings from hospitalizations. Even in that policy debate, focusing solely on expenditures is not warranted. That hospice or hospital-based palliative care teams save money is ethically defensible only if there is improvement in the quality of care and medical decisions are consistent with the informed patient’s wishes and goals of care.
Dr. Teno is a professor at the Brown University School of Public Health. Dr. Gozalo is an associate professor at the university.
Although the study by Obermeyer et al. adds to the evidence regarding hospice care for patients with poor-prognosis cancer, several caveats should be considered. An important threat to the validity of this study was that the unobserved difference in preferences for aggressive care may explain the observed cost savings. Rightfully, the authors acknowledge this and other limitations, such as restriction of the study population to patients with cancer, exclusion of Medicare beneficiaries with managed care and non-Medicare patients, and reliance only on claims-based information for risk adjustments, Dr. Joan M. Teno and Pedro L. Gozalo, Ph.D., both of the Brown University School of Public Health, Providence, R.I., wrote in an editorial accompanying the study.
The findings from this study raise several important policy issues, they said. If hospice saves money, should health care policy promote increased hospice access? Perhaps an even larger policy issue involves the role of costs and not quality in driving U.S. health policy in care of the seriously ill and those at the close of life (JAMA 2014;312:1868-69).
The pressing policy issue in the United States involves not only patients dying of poor-prognosis cancers, but patients with noncancer chronic illness for whom the costs of prolonged hospice stays exceed the potential savings from hospitalizations. Even in that policy debate, focusing solely on expenditures is not warranted. That hospice or hospital-based palliative care teams save money is ethically defensible only if there is improvement in the quality of care and medical decisions are consistent with the informed patient’s wishes and goals of care.
Dr. Teno is a professor at the Brown University School of Public Health. Dr. Gozalo is an associate professor at the university.
Medicare fee-for-service beneficiaries suffering from poor-prognosis cancer who received hospice care were found to have lower rates of hospitalizations, admissions to intensive care units, and invasive procedures than those who did not receive hospice care, according to a study published in JAMA.
“Our findings highlight the potential importance of frank discussions between physicians and patients about the realities of care at the end of life, an issue of particular importance as the Medicare administration weighs decisions around reimbursing physicians for advance care planning,” said Dr. Ziad Obermeyer of the emergency medicine department at Brigham and Women’s Hospital in Boston, and his associates.
In a matched cohort study, Dr. Obermeyer and his colleagues examined the records of 86,851 patients with poor-prognosis cancer – such as brain, pancreatic, and metastatic malignancies – using a nationally representative, 20% sample of Medicare fee-for-service beneficiaries who died in 2011. Of that group, 51,924 individuals (60%) entered hospice care prior to death, with the median time from first diagnosis to death being 13 months (JAMA 2014;312:1888-96).
The researchers then matched patients in hospice vs. nonhospice care, using factors such as age, sex, region, time from first diagnosis to death, and baseline care utilization. Each sample group consisted of 18,165 individuals, with the non–hospice-care group acting as the control. The median hospice duration for the hospice group was 11 days.
Dr. Obermeyer and his associates discovered that hospice beneficiaries had significantly lower rates of hospitalization (42%), intensive care unit admission (15%), invasive procedures (27%), and deaths in hospitals or nursing facilities (14%), compared with their nonhospice counterparts, who had a 65% rate of hospitalization, a 36% rate of intensive care unit admission, a 51% rate of invasive procedures, and a 74% rate of deaths in hospitals or nursing facilities.
Furthermore, the authors found that nonhospice beneficiaries had a higher rate of health care utilization, largely for acute conditions that were not directly related to their cancer, and higher overall costs. On average, costs for hospice beneficiaries were $62,819, while costs for nonhospice beneficiaries were $71,517.
“Hospice enrollment of 5 to 8 weeks produced the greatest savings; shorter stays produced fewer savings, likely because of both hospice initiation costs, and need for intensive symptom palliation in the days before death,” Dr. Obermeyer and his coauthors wrote. “Cost trajectories began to diverge in the week after hospice enrollment, implying that baseline differences between hospice and nonhospice beneficiaries were not responsible for cost differences,” they added.
The study was supported by grants from the National Institutes of Health, the National Cancer Institute, and the Agency for Healthcare Research and Quality. The authors reported no relevant conflicts of interest.
Medicare fee-for-service beneficiaries suffering from poor-prognosis cancer who received hospice care were found to have lower rates of hospitalizations, admissions to intensive care units, and invasive procedures than those who did not receive hospice care, according to a study published in JAMA.
“Our findings highlight the potential importance of frank discussions between physicians and patients about the realities of care at the end of life, an issue of particular importance as the Medicare administration weighs decisions around reimbursing physicians for advance care planning,” said Dr. Ziad Obermeyer of the emergency medicine department at Brigham and Women’s Hospital in Boston, and his associates.
In a matched cohort study, Dr. Obermeyer and his colleagues examined the records of 86,851 patients with poor-prognosis cancer – such as brain, pancreatic, and metastatic malignancies – using a nationally representative, 20% sample of Medicare fee-for-service beneficiaries who died in 2011. Of that group, 51,924 individuals (60%) entered hospice care prior to death, with the median time from first diagnosis to death being 13 months (JAMA 2014;312:1888-96).
The researchers then matched patients in hospice vs. nonhospice care, using factors such as age, sex, region, time from first diagnosis to death, and baseline care utilization. Each sample group consisted of 18,165 individuals, with the non–hospice-care group acting as the control. The median hospice duration for the hospice group was 11 days.
Dr. Obermeyer and his associates discovered that hospice beneficiaries had significantly lower rates of hospitalization (42%), intensive care unit admission (15%), invasive procedures (27%), and deaths in hospitals or nursing facilities (14%), compared with their nonhospice counterparts, who had a 65% rate of hospitalization, a 36% rate of intensive care unit admission, a 51% rate of invasive procedures, and a 74% rate of deaths in hospitals or nursing facilities.
Furthermore, the authors found that nonhospice beneficiaries had a higher rate of health care utilization, largely for acute conditions that were not directly related to their cancer, and higher overall costs. On average, costs for hospice beneficiaries were $62,819, while costs for nonhospice beneficiaries were $71,517.
“Hospice enrollment of 5 to 8 weeks produced the greatest savings; shorter stays produced fewer savings, likely because of both hospice initiation costs, and need for intensive symptom palliation in the days before death,” Dr. Obermeyer and his coauthors wrote. “Cost trajectories began to diverge in the week after hospice enrollment, implying that baseline differences between hospice and nonhospice beneficiaries were not responsible for cost differences,” they added.
The study was supported by grants from the National Institutes of Health, the National Cancer Institute, and the Agency for Healthcare Research and Quality. The authors reported no relevant conflicts of interest.
FROM JAMA
Key clinical point: Medicare beneficiaries with poor-prognosis cancer who received hospice care had lower rates of hospitalization, ICU admission, and invasive procedures than those who did not.
Major finding: Of those receiving hospice care, 42% were admitted to the hospital vs. 65% of those not receiving hospice care.
Data source: Matched cohort study of Medicare fee-for-service beneficiaries.
Disclosures: The study was supported by grants from the National Institutes of Health, the National Cancer Institute, and the Agency for Healthcare Research and Quality. The authors reported no relevant conflicts of interest.
A round-up of ASCO’s 2013-2014 guideline releases, updates, and endorsements
1. Follow-up care, surveillance, and secondary prevention measures for survivors of colorectal cancer1,2
Since 2006, ASCO has adopted a policy of endorsing clinical practice guidelines developed by others in order to increase the number of such guidelines available for ASCO membership. Recently, the society endorsed the guidelines for colon cancer follow-up created by the Cancer Care Ontario (CCO). These guidelines include surveillance recommendations that are very similar to the 2005 ASCO guidelines and the current NCCN guidelines, with a few minor differences. However, unlike NCCN and previous ASCO guidelines, the current guidelines include statements about secondary prevention, written survivorship plans for the patient’s other providers, and the futility of surveillance tests in patients who are not candidates for surgery or systemic therapy due to comorbid disease.
Click on the PDF icon at the top of this introduction to read the full article.
1. Follow-up care, surveillance, and secondary prevention measures for survivors of colorectal cancer1,2
Since 2006, ASCO has adopted a policy of endorsing clinical practice guidelines developed by others in order to increase the number of such guidelines available for ASCO membership. Recently, the society endorsed the guidelines for colon cancer follow-up created by the Cancer Care Ontario (CCO). These guidelines include surveillance recommendations that are very similar to the 2005 ASCO guidelines and the current NCCN guidelines, with a few minor differences. However, unlike NCCN and previous ASCO guidelines, the current guidelines include statements about secondary prevention, written survivorship plans for the patient’s other providers, and the futility of surveillance tests in patients who are not candidates for surgery or systemic therapy due to comorbid disease.
Click on the PDF icon at the top of this introduction to read the full article.
1. Follow-up care, surveillance, and secondary prevention measures for survivors of colorectal cancer1,2
Since 2006, ASCO has adopted a policy of endorsing clinical practice guidelines developed by others in order to increase the number of such guidelines available for ASCO membership. Recently, the society endorsed the guidelines for colon cancer follow-up created by the Cancer Care Ontario (CCO). These guidelines include surveillance recommendations that are very similar to the 2005 ASCO guidelines and the current NCCN guidelines, with a few minor differences. However, unlike NCCN and previous ASCO guidelines, the current guidelines include statements about secondary prevention, written survivorship plans for the patient’s other providers, and the futility of surveillance tests in patients who are not candidates for surgery or systemic therapy due to comorbid disease.
Click on the PDF icon at the top of this introduction to read the full article.
Is choice of anesthesia during cancer surgery linked to outcome?
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Chemotherapy-induced peripheral neuropathy and impact on quality of life 6 months after treatment with chemotherapy
Background Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of cytostatics. With improved survival among cancer patients, CIPN may have a major impact on quality of life (QoL) of cancer survivors.
Objective To determine the occurrence of CIPN induced by oxaliplatin and taxanes and its impact on QoL median 6 months after chemotherapy.
Methods All patients who received their last treatment with oxaliplatin or taxanes in 2 consecutive years in the Máxima Medical Centre, the Netherlands, were eligible for the study. Neurotoxicity and its effect on QoL was assessed with the recently developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) median 6 months after cessation of therapy.
Results Of the 58 eligible patients, 43 (74.1%) completed the questionnaire. After a median follow-up of 6.5 months after cessation of therapy, most of the patients experienced neurotoxicity in the upper and lower extremities (78.8% and 89.7%, respectively). Overall, the most-reported complaints included numbness and tingling in hands as well as feet, suffering from cold feet, and trouble distinguishing objects in the hands. Housekeeping difficulties were reported in 12.8% of patients, and 20.5% of patients became more dependent on others because of the neurotoxicity. Overall, QoL was negatively affected by the impact of CIPN in 48.6% of patients.
Limitations Due to the small sample size selection bias cannot be ruled out and no data about CIPN during treatment were available. Conclusions After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL.
Conclusions After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL.
Funding Floortje Mols was supported by a VENI grant (#451-10-041) from the Netherlands Organization for Scientific Research, The Hague, The Netherlands.
Click on the PDF icon at the top of this introduction to read the full article.
Background Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of cytostatics. With improved survival among cancer patients, CIPN may have a major impact on quality of life (QoL) of cancer survivors.
Objective To determine the occurrence of CIPN induced by oxaliplatin and taxanes and its impact on QoL median 6 months after chemotherapy.
Methods All patients who received their last treatment with oxaliplatin or taxanes in 2 consecutive years in the Máxima Medical Centre, the Netherlands, were eligible for the study. Neurotoxicity and its effect on QoL was assessed with the recently developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) median 6 months after cessation of therapy.
Results Of the 58 eligible patients, 43 (74.1%) completed the questionnaire. After a median follow-up of 6.5 months after cessation of therapy, most of the patients experienced neurotoxicity in the upper and lower extremities (78.8% and 89.7%, respectively). Overall, the most-reported complaints included numbness and tingling in hands as well as feet, suffering from cold feet, and trouble distinguishing objects in the hands. Housekeeping difficulties were reported in 12.8% of patients, and 20.5% of patients became more dependent on others because of the neurotoxicity. Overall, QoL was negatively affected by the impact of CIPN in 48.6% of patients.
Limitations Due to the small sample size selection bias cannot be ruled out and no data about CIPN during treatment were available. Conclusions After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL.
Conclusions After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL.
Funding Floortje Mols was supported by a VENI grant (#451-10-041) from the Netherlands Organization for Scientific Research, The Hague, The Netherlands.
Click on the PDF icon at the top of this introduction to read the full article.
Background Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of cytostatics. With improved survival among cancer patients, CIPN may have a major impact on quality of life (QoL) of cancer survivors.
Objective To determine the occurrence of CIPN induced by oxaliplatin and taxanes and its impact on QoL median 6 months after chemotherapy.
Methods All patients who received their last treatment with oxaliplatin or taxanes in 2 consecutive years in the Máxima Medical Centre, the Netherlands, were eligible for the study. Neurotoxicity and its effect on QoL was assessed with the recently developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) median 6 months after cessation of therapy.
Results Of the 58 eligible patients, 43 (74.1%) completed the questionnaire. After a median follow-up of 6.5 months after cessation of therapy, most of the patients experienced neurotoxicity in the upper and lower extremities (78.8% and 89.7%, respectively). Overall, the most-reported complaints included numbness and tingling in hands as well as feet, suffering from cold feet, and trouble distinguishing objects in the hands. Housekeeping difficulties were reported in 12.8% of patients, and 20.5% of patients became more dependent on others because of the neurotoxicity. Overall, QoL was negatively affected by the impact of CIPN in 48.6% of patients.
Limitations Due to the small sample size selection bias cannot be ruled out and no data about CIPN during treatment were available. Conclusions After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL.
Conclusions After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL.
Funding Floortje Mols was supported by a VENI grant (#451-10-041) from the Netherlands Organization for Scientific Research, The Hague, The Netherlands.
Click on the PDF icon at the top of this introduction to read the full article.
Impact of aprepitant on emesis control, dose intensity, and recurrence-free survival in a population-based cohort of head and neck cancer patients receiving high-dose cisplatin chemotherapy
Objective To evaluate the impact of aprepitant on emesis control, DI, and RFS.
Methods HNC patients treated at the British Columbia Cancer Agency were analyzed. Kaplan-Meier method and adjusted Cox proportional hazard models were used to evaluate RFS in aprepitant users. To control for selection bias, a propensity score analysis was conducted.
Results A total of 192 HNC patients were included: 141 received aprepitant prophylaxis. The aprepitant-treated and untreated groups were comparable in mean age (56.3 vs 58.1 years), male gender (82.3% vs 86.3%), tumor location, and number of metastatic sites. However, more patients in the aprepitant group than in the untreated group had surgically resectable disease (31.2% vs 15.7%, respectively) and better performance status (ECOG 0/1, 87.9% vs 76.4%). Less emesis was reported in the aprepitant group (21.3% vs 28.0%). Patients in the treated group were also more likely to complete 3 cycles of high-dose cisplatin (OR, 2.3; P = .03). The propensity score adjusted Cox regression analysis suggested a reduced risk of disease recurrence in patients who received aprepitant (HR, 0.47; 95% CI, 0.17- 1.28).
Limitations Potential confounders such as other diseases or treatments that may have influenced the presence of nausea/emesis symptoms.
Conclusion Aprepitant contributed to improved emesis control, enhanced DI, and better adherence to cisplatin chemotherapy.
Funding/sponsorship The British Columbia Cancer Foundation and Canadian Cancer Society Research Institute.
Click on the PDF icon at the top of this introduction to read the full article.
Objective To evaluate the impact of aprepitant on emesis control, DI, and RFS.
Methods HNC patients treated at the British Columbia Cancer Agency were analyzed. Kaplan-Meier method and adjusted Cox proportional hazard models were used to evaluate RFS in aprepitant users. To control for selection bias, a propensity score analysis was conducted.
Results A total of 192 HNC patients were included: 141 received aprepitant prophylaxis. The aprepitant-treated and untreated groups were comparable in mean age (56.3 vs 58.1 years), male gender (82.3% vs 86.3%), tumor location, and number of metastatic sites. However, more patients in the aprepitant group than in the untreated group had surgically resectable disease (31.2% vs 15.7%, respectively) and better performance status (ECOG 0/1, 87.9% vs 76.4%). Less emesis was reported in the aprepitant group (21.3% vs 28.0%). Patients in the treated group were also more likely to complete 3 cycles of high-dose cisplatin (OR, 2.3; P = .03). The propensity score adjusted Cox regression analysis suggested a reduced risk of disease recurrence in patients who received aprepitant (HR, 0.47; 95% CI, 0.17- 1.28).
Limitations Potential confounders such as other diseases or treatments that may have influenced the presence of nausea/emesis symptoms.
Conclusion Aprepitant contributed to improved emesis control, enhanced DI, and better adherence to cisplatin chemotherapy.
Funding/sponsorship The British Columbia Cancer Foundation and Canadian Cancer Society Research Institute.
Click on the PDF icon at the top of this introduction to read the full article.
Objective To evaluate the impact of aprepitant on emesis control, DI, and RFS.
Methods HNC patients treated at the British Columbia Cancer Agency were analyzed. Kaplan-Meier method and adjusted Cox proportional hazard models were used to evaluate RFS in aprepitant users. To control for selection bias, a propensity score analysis was conducted.
Results A total of 192 HNC patients were included: 141 received aprepitant prophylaxis. The aprepitant-treated and untreated groups were comparable in mean age (56.3 vs 58.1 years), male gender (82.3% vs 86.3%), tumor location, and number of metastatic sites. However, more patients in the aprepitant group than in the untreated group had surgically resectable disease (31.2% vs 15.7%, respectively) and better performance status (ECOG 0/1, 87.9% vs 76.4%). Less emesis was reported in the aprepitant group (21.3% vs 28.0%). Patients in the treated group were also more likely to complete 3 cycles of high-dose cisplatin (OR, 2.3; P = .03). The propensity score adjusted Cox regression analysis suggested a reduced risk of disease recurrence in patients who received aprepitant (HR, 0.47; 95% CI, 0.17- 1.28).
Limitations Potential confounders such as other diseases or treatments that may have influenced the presence of nausea/emesis symptoms.
Conclusion Aprepitant contributed to improved emesis control, enhanced DI, and better adherence to cisplatin chemotherapy.
Funding/sponsorship The British Columbia Cancer Foundation and Canadian Cancer Society Research Institute.
Click on the PDF icon at the top of this introduction to read the full article.
Congestive heart failure during induction with anthracycline-based therapy in patients with acute promyelocytic leukemia
Background Acute promyelocytic leukemia (APL) is a highly curable malignancy. However, 30% of patients die during therapy induction from bleeding, differentiation syndrome (DS), and/or infection. Recommendations suggest that congestive heart failure (CHF) is a presenting feature of DS.
Objective To assess the incidence of CHF during induction in patients with APL.
Methods A retrospective chart review was performed of patients diagnosed with APL from December 2004 to July 2013 and managed at Georgia Regents University Cancer Center. Baseline and follow-up ejection fractions (EF) were recorded and patients with a drop in EF during the induction period were evaluated.
Results Of the 40 evaluable patients, 37 received idarubicin-based chemotherapy. 16 of the 37 patients had a repeat ECHO for suspected cardiomyopathy, and 6 of the 16 patients (37.5%) demonstrated a decrease in EF (absolute drop, 10%-35%). The cardiac function recovered completely in 4 patients and partially in 1 patient. Gender, history of hypertension, and body mass index did not seem to correlate with incidence of CHF.
Limitations The patient population is very small given the rarity of the disease. Present practice patterns do not routinely address CHF in the differential diagnosis.
Conclusions Patients with APL are at risk for cardiac toxicity for a number of reasons, including cytokine storm and inflammatory state, use of anthracyclines, and DS. The clinical presentation of DS most commonly involves dyspnea and fluid retention, which are also symptoms of heart failure. Prompt cardiac evaluation should be undertaken to rule out CHF in APL patients who are going to receive an anthracycline-based therapy, because early intervention may result in an improved outcome.
Click on the PDF icon at the top of this introduction to read the full article.
Background Acute promyelocytic leukemia (APL) is a highly curable malignancy. However, 30% of patients die during therapy induction from bleeding, differentiation syndrome (DS), and/or infection. Recommendations suggest that congestive heart failure (CHF) is a presenting feature of DS.
Objective To assess the incidence of CHF during induction in patients with APL.
Methods A retrospective chart review was performed of patients diagnosed with APL from December 2004 to July 2013 and managed at Georgia Regents University Cancer Center. Baseline and follow-up ejection fractions (EF) were recorded and patients with a drop in EF during the induction period were evaluated.
Results Of the 40 evaluable patients, 37 received idarubicin-based chemotherapy. 16 of the 37 patients had a repeat ECHO for suspected cardiomyopathy, and 6 of the 16 patients (37.5%) demonstrated a decrease in EF (absolute drop, 10%-35%). The cardiac function recovered completely in 4 patients and partially in 1 patient. Gender, history of hypertension, and body mass index did not seem to correlate with incidence of CHF.
Limitations The patient population is very small given the rarity of the disease. Present practice patterns do not routinely address CHF in the differential diagnosis.
Conclusions Patients with APL are at risk for cardiac toxicity for a number of reasons, including cytokine storm and inflammatory state, use of anthracyclines, and DS. The clinical presentation of DS most commonly involves dyspnea and fluid retention, which are also symptoms of heart failure. Prompt cardiac evaluation should be undertaken to rule out CHF in APL patients who are going to receive an anthracycline-based therapy, because early intervention may result in an improved outcome.
Click on the PDF icon at the top of this introduction to read the full article.
Background Acute promyelocytic leukemia (APL) is a highly curable malignancy. However, 30% of patients die during therapy induction from bleeding, differentiation syndrome (DS), and/or infection. Recommendations suggest that congestive heart failure (CHF) is a presenting feature of DS.
Objective To assess the incidence of CHF during induction in patients with APL.
Methods A retrospective chart review was performed of patients diagnosed with APL from December 2004 to July 2013 and managed at Georgia Regents University Cancer Center. Baseline and follow-up ejection fractions (EF) were recorded and patients with a drop in EF during the induction period were evaluated.
Results Of the 40 evaluable patients, 37 received idarubicin-based chemotherapy. 16 of the 37 patients had a repeat ECHO for suspected cardiomyopathy, and 6 of the 16 patients (37.5%) demonstrated a decrease in EF (absolute drop, 10%-35%). The cardiac function recovered completely in 4 patients and partially in 1 patient. Gender, history of hypertension, and body mass index did not seem to correlate with incidence of CHF.
Limitations The patient population is very small given the rarity of the disease. Present practice patterns do not routinely address CHF in the differential diagnosis.
Conclusions Patients with APL are at risk for cardiac toxicity for a number of reasons, including cytokine storm and inflammatory state, use of anthracyclines, and DS. The clinical presentation of DS most commonly involves dyspnea and fluid retention, which are also symptoms of heart failure. Prompt cardiac evaluation should be undertaken to rule out CHF in APL patients who are going to receive an anthracycline-based therapy, because early intervention may result in an improved outcome.
Click on the PDF icon at the top of this introduction to read the full article.
A wonderful life
Who will get cancer treatment-induced cardiotoxicity?
LAS VEGAS – The search is on for predictors of which cancer patients will experience treatment-induced cardiotoxicity, and an initial report from the PREDICT study has identified several.
One predictor is the patient’s type of cancer. In PREDICT, patients with lymphoma had a twofold greater risk of developing treatment-related cardiotoxicity, compared with those with breast cancer. Moreover, those with a cancer diagnosis other than lymphoma or breast cancer had a fivefold greater risk than breast cancer patients, Dr. Daniel J. Lenihan reported at the annual meeting of the Heart Failure Society of America.
“It’s important to know that many of the studies on cardiotoxicity risk have been done in breast cancer patients. There are a lot of other cancer patients out there,” observed Dr. Lenihan, professor of medicine and director of clinical research in the division of cardiovascular medicine at Vanderbilt University in Nashville.
PREDICT is a prospective, community-based study of 597 cancer patients undergoing anthracycline-based chemotherapy in 24 community oncology programs. It is primarily a study of the effectiveness of using cardiac biomarkers to predict cardiotoxicity, along with an analysis of the results of various forms of treatment of the cardiotoxicity.
During up to 12 months of follow-up 11% of PREDICT participants experienced a cardiac event, most commonly symptomatic heart failure or a greater than 10% drop in left ventricular ejection fraction, which took a patient from normal range to below normal. Another impressive finding was the substantial burden of conventional cardiovascular risk factors present at baseline in patients scheduled for anthracycline-based chemotherapy. In a multivariate logistic regression analysis, the higher a cancer patient’s cardiovascular risk factor level, the greater the likelihood of chemotherapy-related cardiotoxicity.
A baseline B-type natriuretic peptide (BNP) level in excess of 100 pg/mL was a powerful predictor of a chemotherapy-related cardiac event, with an associated 2.1-fold increased risk. As a predictor of cardiotoxicity during the study period, baseline BNP had a sensitivity of 35%, a specificity of 85%, a positive predictive value of 22%, and – most importantly – a negative predictive value of 92%, according to Dr. Lenihan.
Similarly, using as cutoffs either a baseline BNP greater than 100 pg/mL or a troponin greater than 0.05 ng/mL had a sensitivity of 60%, a specificity of 50%, a positive predictive value of 13%, and a negative predictive value of 91%, he continued.
Myocardial imaging as a tool for predicting which patients will develop cardiotoxicity during or after cancer therapy is another active area of investigation. Other investigators have shown that myocardial strain imaging holds considerable promise (J. Am. Coll. Cardiol. 2014;63:2751-68); however, it’s not terribly practical because many echocardiography laboratories balk at the idea of routinely performing serial strain imaging studies in all cancer patients, Dr. Lenihan said.
Practical predictors of increased risk for cancer therapy-related cardiotoxicity are sorely needed in order to identify candidates for prophylaxis with an agent such as dexrazoxane, which has been shown in a meta-analysis to reduce the risk of clinical or subclinical heart failure by 71% (Cochrane Database Syst. Review 2008; April 16:CD003917).
Another promising preventive approach was displayed in the Spanish OVERCOME trial, involving 90 patients undergoing intensive chemotherapy for malignant hemopathies. Those randomized to combined prophylaxis with enalapril plus carvedilol had a 6.7% rate of the composite endpoint of death, heart failure, or an LVEF below 45% at 6 months, compared with 24.4% in controls (J. Am. Coll. Cardiol. 2013;61:2355-62).
Also, predictors of increased risk are helpful in identifying cancer therapy–related cardiotoxicity early in its course, when aggressive treatment with standard heart failure medications such as beta blockers and ACE inhibitors is most likely to be beneficial.
“Everybody in cardiology is used to the concept that time is muscle: don’t let ischemia persist. Have a strategy to resolve it as soon as possible. That paradigm really can also apply to chemotherapy-related injury: the longer you leave it alone, the more permanent it becomes. Being able to detect it at its earliest stage is critically important,” according to Dr. Lenihan.
He cited as an example a study of 201 consecutive patients with anthracycline-induced cardiomyopathy conducted at the European Institute of Oncology in Milan. The conventional dogma is that anthracycline-induced cardiomyopathy is typically permanent, but this study showed that’s not true.
When treatment with enalapril and carvedilol was initiated within the first couple of months following the end of chemotherapy, 64% of patients experienced complete recovery of their LVEF. When the heart failure medications were commenced 3-4 months after completing chemotherapy, the LVEF recovery rate dropped to 28%. No complete recovery of LVEF occurred in patients who began enalapril plus carvedilol after 6 months (J. Am. Coll. Cardiol. 2010;55:213-20).
“There is a real opportunity here to improve the care of cancer patients and prevent heart failure,” Dr. Lenihan concluded.
He reported receiving research support from Singulex, Millenium, and Acorda as well as serving as a consultant to Onyx and Roche.
LAS VEGAS – The search is on for predictors of which cancer patients will experience treatment-induced cardiotoxicity, and an initial report from the PREDICT study has identified several.
One predictor is the patient’s type of cancer. In PREDICT, patients with lymphoma had a twofold greater risk of developing treatment-related cardiotoxicity, compared with those with breast cancer. Moreover, those with a cancer diagnosis other than lymphoma or breast cancer had a fivefold greater risk than breast cancer patients, Dr. Daniel J. Lenihan reported at the annual meeting of the Heart Failure Society of America.
“It’s important to know that many of the studies on cardiotoxicity risk have been done in breast cancer patients. There are a lot of other cancer patients out there,” observed Dr. Lenihan, professor of medicine and director of clinical research in the division of cardiovascular medicine at Vanderbilt University in Nashville.
PREDICT is a prospective, community-based study of 597 cancer patients undergoing anthracycline-based chemotherapy in 24 community oncology programs. It is primarily a study of the effectiveness of using cardiac biomarkers to predict cardiotoxicity, along with an analysis of the results of various forms of treatment of the cardiotoxicity.
During up to 12 months of follow-up 11% of PREDICT participants experienced a cardiac event, most commonly symptomatic heart failure or a greater than 10% drop in left ventricular ejection fraction, which took a patient from normal range to below normal. Another impressive finding was the substantial burden of conventional cardiovascular risk factors present at baseline in patients scheduled for anthracycline-based chemotherapy. In a multivariate logistic regression analysis, the higher a cancer patient’s cardiovascular risk factor level, the greater the likelihood of chemotherapy-related cardiotoxicity.
A baseline B-type natriuretic peptide (BNP) level in excess of 100 pg/mL was a powerful predictor of a chemotherapy-related cardiac event, with an associated 2.1-fold increased risk. As a predictor of cardiotoxicity during the study period, baseline BNP had a sensitivity of 35%, a specificity of 85%, a positive predictive value of 22%, and – most importantly – a negative predictive value of 92%, according to Dr. Lenihan.
Similarly, using as cutoffs either a baseline BNP greater than 100 pg/mL or a troponin greater than 0.05 ng/mL had a sensitivity of 60%, a specificity of 50%, a positive predictive value of 13%, and a negative predictive value of 91%, he continued.
Myocardial imaging as a tool for predicting which patients will develop cardiotoxicity during or after cancer therapy is another active area of investigation. Other investigators have shown that myocardial strain imaging holds considerable promise (J. Am. Coll. Cardiol. 2014;63:2751-68); however, it’s not terribly practical because many echocardiography laboratories balk at the idea of routinely performing serial strain imaging studies in all cancer patients, Dr. Lenihan said.
Practical predictors of increased risk for cancer therapy-related cardiotoxicity are sorely needed in order to identify candidates for prophylaxis with an agent such as dexrazoxane, which has been shown in a meta-analysis to reduce the risk of clinical or subclinical heart failure by 71% (Cochrane Database Syst. Review 2008; April 16:CD003917).
Another promising preventive approach was displayed in the Spanish OVERCOME trial, involving 90 patients undergoing intensive chemotherapy for malignant hemopathies. Those randomized to combined prophylaxis with enalapril plus carvedilol had a 6.7% rate of the composite endpoint of death, heart failure, or an LVEF below 45% at 6 months, compared with 24.4% in controls (J. Am. Coll. Cardiol. 2013;61:2355-62).
Also, predictors of increased risk are helpful in identifying cancer therapy–related cardiotoxicity early in its course, when aggressive treatment with standard heart failure medications such as beta blockers and ACE inhibitors is most likely to be beneficial.
“Everybody in cardiology is used to the concept that time is muscle: don’t let ischemia persist. Have a strategy to resolve it as soon as possible. That paradigm really can also apply to chemotherapy-related injury: the longer you leave it alone, the more permanent it becomes. Being able to detect it at its earliest stage is critically important,” according to Dr. Lenihan.
He cited as an example a study of 201 consecutive patients with anthracycline-induced cardiomyopathy conducted at the European Institute of Oncology in Milan. The conventional dogma is that anthracycline-induced cardiomyopathy is typically permanent, but this study showed that’s not true.
When treatment with enalapril and carvedilol was initiated within the first couple of months following the end of chemotherapy, 64% of patients experienced complete recovery of their LVEF. When the heart failure medications were commenced 3-4 months after completing chemotherapy, the LVEF recovery rate dropped to 28%. No complete recovery of LVEF occurred in patients who began enalapril plus carvedilol after 6 months (J. Am. Coll. Cardiol. 2010;55:213-20).
“There is a real opportunity here to improve the care of cancer patients and prevent heart failure,” Dr. Lenihan concluded.
He reported receiving research support from Singulex, Millenium, and Acorda as well as serving as a consultant to Onyx and Roche.
LAS VEGAS – The search is on for predictors of which cancer patients will experience treatment-induced cardiotoxicity, and an initial report from the PREDICT study has identified several.
One predictor is the patient’s type of cancer. In PREDICT, patients with lymphoma had a twofold greater risk of developing treatment-related cardiotoxicity, compared with those with breast cancer. Moreover, those with a cancer diagnosis other than lymphoma or breast cancer had a fivefold greater risk than breast cancer patients, Dr. Daniel J. Lenihan reported at the annual meeting of the Heart Failure Society of America.
“It’s important to know that many of the studies on cardiotoxicity risk have been done in breast cancer patients. There are a lot of other cancer patients out there,” observed Dr. Lenihan, professor of medicine and director of clinical research in the division of cardiovascular medicine at Vanderbilt University in Nashville.
PREDICT is a prospective, community-based study of 597 cancer patients undergoing anthracycline-based chemotherapy in 24 community oncology programs. It is primarily a study of the effectiveness of using cardiac biomarkers to predict cardiotoxicity, along with an analysis of the results of various forms of treatment of the cardiotoxicity.
During up to 12 months of follow-up 11% of PREDICT participants experienced a cardiac event, most commonly symptomatic heart failure or a greater than 10% drop in left ventricular ejection fraction, which took a patient from normal range to below normal. Another impressive finding was the substantial burden of conventional cardiovascular risk factors present at baseline in patients scheduled for anthracycline-based chemotherapy. In a multivariate logistic regression analysis, the higher a cancer patient’s cardiovascular risk factor level, the greater the likelihood of chemotherapy-related cardiotoxicity.
A baseline B-type natriuretic peptide (BNP) level in excess of 100 pg/mL was a powerful predictor of a chemotherapy-related cardiac event, with an associated 2.1-fold increased risk. As a predictor of cardiotoxicity during the study period, baseline BNP had a sensitivity of 35%, a specificity of 85%, a positive predictive value of 22%, and – most importantly – a negative predictive value of 92%, according to Dr. Lenihan.
Similarly, using as cutoffs either a baseline BNP greater than 100 pg/mL or a troponin greater than 0.05 ng/mL had a sensitivity of 60%, a specificity of 50%, a positive predictive value of 13%, and a negative predictive value of 91%, he continued.
Myocardial imaging as a tool for predicting which patients will develop cardiotoxicity during or after cancer therapy is another active area of investigation. Other investigators have shown that myocardial strain imaging holds considerable promise (J. Am. Coll. Cardiol. 2014;63:2751-68); however, it’s not terribly practical because many echocardiography laboratories balk at the idea of routinely performing serial strain imaging studies in all cancer patients, Dr. Lenihan said.
Practical predictors of increased risk for cancer therapy-related cardiotoxicity are sorely needed in order to identify candidates for prophylaxis with an agent such as dexrazoxane, which has been shown in a meta-analysis to reduce the risk of clinical or subclinical heart failure by 71% (Cochrane Database Syst. Review 2008; April 16:CD003917).
Another promising preventive approach was displayed in the Spanish OVERCOME trial, involving 90 patients undergoing intensive chemotherapy for malignant hemopathies. Those randomized to combined prophylaxis with enalapril plus carvedilol had a 6.7% rate of the composite endpoint of death, heart failure, or an LVEF below 45% at 6 months, compared with 24.4% in controls (J. Am. Coll. Cardiol. 2013;61:2355-62).
Also, predictors of increased risk are helpful in identifying cancer therapy–related cardiotoxicity early in its course, when aggressive treatment with standard heart failure medications such as beta blockers and ACE inhibitors is most likely to be beneficial.
“Everybody in cardiology is used to the concept that time is muscle: don’t let ischemia persist. Have a strategy to resolve it as soon as possible. That paradigm really can also apply to chemotherapy-related injury: the longer you leave it alone, the more permanent it becomes. Being able to detect it at its earliest stage is critically important,” according to Dr. Lenihan.
He cited as an example a study of 201 consecutive patients with anthracycline-induced cardiomyopathy conducted at the European Institute of Oncology in Milan. The conventional dogma is that anthracycline-induced cardiomyopathy is typically permanent, but this study showed that’s not true.
When treatment with enalapril and carvedilol was initiated within the first couple of months following the end of chemotherapy, 64% of patients experienced complete recovery of their LVEF. When the heart failure medications were commenced 3-4 months after completing chemotherapy, the LVEF recovery rate dropped to 28%. No complete recovery of LVEF occurred in patients who began enalapril plus carvedilol after 6 months (J. Am. Coll. Cardiol. 2010;55:213-20).
“There is a real opportunity here to improve the care of cancer patients and prevent heart failure,” Dr. Lenihan concluded.
He reported receiving research support from Singulex, Millenium, and Acorda as well as serving as a consultant to Onyx and Roche.
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point: An elevated baseline B-type natriuretic peptide or troponin level identifies cancer patients at increased risk of cardiotoxicity during anthracycline-based chemotherapy.
Major finding: Cancer patients with a BNP level greater than 100 pg/mL prior to going on anthracycline-based chemotherapy were 2.1-fold more likely to develop treatment-related cardiotoxicity.
Data source: The prospective PREDICT study includes roughly 600 patients undergoing anthracycline-based chemotherapy at 24 community cancer centers.
Disclosures: The study is sponsored by M.D. Anderson Cancer Center. The presenter reported serving as a consultant to Onyx and Roche.
