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Research and Reviews for the Practicing Oncologist
Conventional chemo bests tyrosine kinase inhibitors in wild-type lung cancers
Conventional chemotherapy prolonged progression-free survival and induced a higher tumor response rate, compared with tyrosine kinase inhibitors, in a meta-analysis involving 1,605 patients with advanced wild-type non–small cell lung cancer, according to a report published online April 8 in JAMA.
First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as erlotinib and gefitinib are first-line treatments for non–small cell lung cancers that are known to harbor EGFR-activating mutations, but their benefit is less pronounced against wild-type NSCLCs (no mutation detected in the EGFR gene). Several small studies assessing the efficacy of these agents in wild-type NSCLCs have produced inconclusive results, mostly because of the small number of participating patients, said Dr. June-Koo Lee of the department of internal medicine, Seoul (Republic of Korea) National University Hospital, and associates.
The investigators therefore pooled data from a meta-analysis of 11 randomized, controlled, open-label trials, to obtain sufficient data to compare EGFR tyrosine kinase inhibitors (811 patients) against conventional chemotherapeutic agents such as cisplatin, carboplatin, docetaxel, and pemetrexed (794 patients) in wild-type NSCLCs.
Progression-free survival was significantly longer with conventional chemotherapy than with EGFR tyrosine kinase inhibitors (6.4 vs 1.9 months; hazard ratio, 1.41; 95% confidence interval, 1.10-1.81). Conventional chemotherapy also induced a significantly higher objective response rate than did tyrosine kinase inhibitors (16.8% vs 7.2%; relative risk of nonresponse from tyrosine kinase inhibitors, 1.11; 95% CI, 1.02-1.21).
Overall survival was not significantly different between the two study groups, but that "can be explained by the large crossover rates of the included trials," Dr. Lee and associates reported (JAMA 2014;311:1430-7).
The findings "suggest that current guidelines recommending EGFR tyrosine kinase inhibitors as a standard treatment in this setting ... may need to be reevaluated," they wrote.
However, it is important to note that a treatment’s toxicity profile is crucial when choosing among different options, and EGFR tyrosine kinase inhibitors are known to have a better toxicity profile than standard chemotherapeutic agents. They should therefore be considered for certain patients, such as those who have a poor performance status, the investigators said.
This study was supported in part by the National Research Foundation of Korea. Dr. Lee reported no financial conflicts of interest; two coauthors reported ties to Pfizer, Lilly, and other companies.
Conventional chemotherapy prolonged progression-free survival and induced a higher tumor response rate, compared with tyrosine kinase inhibitors, in a meta-analysis involving 1,605 patients with advanced wild-type non–small cell lung cancer, according to a report published online April 8 in JAMA.
First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as erlotinib and gefitinib are first-line treatments for non–small cell lung cancers that are known to harbor EGFR-activating mutations, but their benefit is less pronounced against wild-type NSCLCs (no mutation detected in the EGFR gene). Several small studies assessing the efficacy of these agents in wild-type NSCLCs have produced inconclusive results, mostly because of the small number of participating patients, said Dr. June-Koo Lee of the department of internal medicine, Seoul (Republic of Korea) National University Hospital, and associates.
The investigators therefore pooled data from a meta-analysis of 11 randomized, controlled, open-label trials, to obtain sufficient data to compare EGFR tyrosine kinase inhibitors (811 patients) against conventional chemotherapeutic agents such as cisplatin, carboplatin, docetaxel, and pemetrexed (794 patients) in wild-type NSCLCs.
Progression-free survival was significantly longer with conventional chemotherapy than with EGFR tyrosine kinase inhibitors (6.4 vs 1.9 months; hazard ratio, 1.41; 95% confidence interval, 1.10-1.81). Conventional chemotherapy also induced a significantly higher objective response rate than did tyrosine kinase inhibitors (16.8% vs 7.2%; relative risk of nonresponse from tyrosine kinase inhibitors, 1.11; 95% CI, 1.02-1.21).
Overall survival was not significantly different between the two study groups, but that "can be explained by the large crossover rates of the included trials," Dr. Lee and associates reported (JAMA 2014;311:1430-7).
The findings "suggest that current guidelines recommending EGFR tyrosine kinase inhibitors as a standard treatment in this setting ... may need to be reevaluated," they wrote.
However, it is important to note that a treatment’s toxicity profile is crucial when choosing among different options, and EGFR tyrosine kinase inhibitors are known to have a better toxicity profile than standard chemotherapeutic agents. They should therefore be considered for certain patients, such as those who have a poor performance status, the investigators said.
This study was supported in part by the National Research Foundation of Korea. Dr. Lee reported no financial conflicts of interest; two coauthors reported ties to Pfizer, Lilly, and other companies.
Conventional chemotherapy prolonged progression-free survival and induced a higher tumor response rate, compared with tyrosine kinase inhibitors, in a meta-analysis involving 1,605 patients with advanced wild-type non–small cell lung cancer, according to a report published online April 8 in JAMA.
First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as erlotinib and gefitinib are first-line treatments for non–small cell lung cancers that are known to harbor EGFR-activating mutations, but their benefit is less pronounced against wild-type NSCLCs (no mutation detected in the EGFR gene). Several small studies assessing the efficacy of these agents in wild-type NSCLCs have produced inconclusive results, mostly because of the small number of participating patients, said Dr. June-Koo Lee of the department of internal medicine, Seoul (Republic of Korea) National University Hospital, and associates.
The investigators therefore pooled data from a meta-analysis of 11 randomized, controlled, open-label trials, to obtain sufficient data to compare EGFR tyrosine kinase inhibitors (811 patients) against conventional chemotherapeutic agents such as cisplatin, carboplatin, docetaxel, and pemetrexed (794 patients) in wild-type NSCLCs.
Progression-free survival was significantly longer with conventional chemotherapy than with EGFR tyrosine kinase inhibitors (6.4 vs 1.9 months; hazard ratio, 1.41; 95% confidence interval, 1.10-1.81). Conventional chemotherapy also induced a significantly higher objective response rate than did tyrosine kinase inhibitors (16.8% vs 7.2%; relative risk of nonresponse from tyrosine kinase inhibitors, 1.11; 95% CI, 1.02-1.21).
Overall survival was not significantly different between the two study groups, but that "can be explained by the large crossover rates of the included trials," Dr. Lee and associates reported (JAMA 2014;311:1430-7).
The findings "suggest that current guidelines recommending EGFR tyrosine kinase inhibitors as a standard treatment in this setting ... may need to be reevaluated," they wrote.
However, it is important to note that a treatment’s toxicity profile is crucial when choosing among different options, and EGFR tyrosine kinase inhibitors are known to have a better toxicity profile than standard chemotherapeutic agents. They should therefore be considered for certain patients, such as those who have a poor performance status, the investigators said.
This study was supported in part by the National Research Foundation of Korea. Dr. Lee reported no financial conflicts of interest; two coauthors reported ties to Pfizer, Lilly, and other companies.
FROM JAMA
Key clinical point:
Major finding: Progression-free survival was significantly longer with conventional chemotherapy than with EGFR tyrosine kinase inhibitors (6.4 vs. 1.9 months), and the objective response rate was significantly higher (16.8% vs. 7.2%).
Data source: A review of the literature and meta-analysis of 11 prospective, open-label, randomized controlled trials involving 1,605 patients with wild-type NSCLC who were treated with either first-generation EGFR tyrosine kinase inhibitors (erlotinib or gefitinib) or conventional chemotherapy (cisplatin, carboplatin, docetaxel, or pemetrexed).
Disclosures: This study was supported in part by the National Research Foundation of Korea. Dr. Lee reported no financial conflicts of interest; two coauthors reported ties to Pfizer, Lilly, and other companies.
Biomarkers in urine outperformed cytology and cytoscopy
A DNA methylation marker panel from urine sediments was superior to gold standard tests for predicting recurrence of bladder cancer, investigators reported April 1 in Clinical Cancer Research.
Eighty percent of patients with positive scores on the three-marker panel developed recurrent, biopsy-proven urothelial carcinoma after complete resection of the visible primary tumor (95% confidence interval, 62%-98%), reported Dr. Sheng-Fang Su of University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.
The panel’s positive predictive value far exceeded the values for cytology (35%; 95% CI, 14%-56%) and cytoscopy (15%; 95% CI, 0-31%), the investigators reported (Clin. Cancer Res. 2014 [doi:10.1158/1078-0432.CCR-13-2637]).
The prospective study enrolled 90 patients who had undergone transurethral resection of noninvasive urothelial carcinomas (Tis, Ta, T1; grade low high). Median age of patients was 69 years (range, 41-96). Patients with high-grade Ta/T1 tumors had received intravesical Bacillus Calmette-Guerin vaccine or mitomycin C at their physicians’ discretion.
The investigators performed cytology and extracted DNA from 368 urine and bladder wash specimens collected from patients over a seven-year period. Patients also underwent cytoscopy. The investigators used logistic regression to assess the sensitivity and specificity of various combinations of DNA methylation markers.
The optimal panel included a tumor-specific hypermethylated marker (SOX1), an epigenetic marker (IRAK3), and a field defect-associated hypomethylated marker (L1-MET), the researchers said. The panel’s sensitivity was 80% (95% CI, 60%-96%) and specificity was 97% (95% CI, 91%-100%), they reported. The negative predictive value of the panel (74%) resembled that of cytoscopy (80%) and cytology (76%), they said.
Dr. Su and his associates noted that previous marker tests were more sensitive than cytology, including the FDA-approved NMP-22, ImmunoCyst, and UroVysion tests. But these are expensive, labor-intensive, less specific, and benign urinary conditions can compromise their reliability, they added.
A panel like the one used in the study could help clinicians determine the appropriate frequency of follow-up cytology after bladder cancer resection, the investigators said. But they noted that the validation sets were not ideal and that the urine markers should be further explored in a larger, independent cohort.
The National Cancer Institute funded the research. One of the researchers, Dr. Jones, reported having been a consultant and advisory board member of Astex, Lilly, and Zymo. The other authors reported no conflicts of interest.
A DNA methylation marker panel from urine sediments was superior to gold standard tests for predicting recurrence of bladder cancer, investigators reported April 1 in Clinical Cancer Research.
Eighty percent of patients with positive scores on the three-marker panel developed recurrent, biopsy-proven urothelial carcinoma after complete resection of the visible primary tumor (95% confidence interval, 62%-98%), reported Dr. Sheng-Fang Su of University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.
The panel’s positive predictive value far exceeded the values for cytology (35%; 95% CI, 14%-56%) and cytoscopy (15%; 95% CI, 0-31%), the investigators reported (Clin. Cancer Res. 2014 [doi:10.1158/1078-0432.CCR-13-2637]).
The prospective study enrolled 90 patients who had undergone transurethral resection of noninvasive urothelial carcinomas (Tis, Ta, T1; grade low high). Median age of patients was 69 years (range, 41-96). Patients with high-grade Ta/T1 tumors had received intravesical Bacillus Calmette-Guerin vaccine or mitomycin C at their physicians’ discretion.
The investigators performed cytology and extracted DNA from 368 urine and bladder wash specimens collected from patients over a seven-year period. Patients also underwent cytoscopy. The investigators used logistic regression to assess the sensitivity and specificity of various combinations of DNA methylation markers.
The optimal panel included a tumor-specific hypermethylated marker (SOX1), an epigenetic marker (IRAK3), and a field defect-associated hypomethylated marker (L1-MET), the researchers said. The panel’s sensitivity was 80% (95% CI, 60%-96%) and specificity was 97% (95% CI, 91%-100%), they reported. The negative predictive value of the panel (74%) resembled that of cytoscopy (80%) and cytology (76%), they said.
Dr. Su and his associates noted that previous marker tests were more sensitive than cytology, including the FDA-approved NMP-22, ImmunoCyst, and UroVysion tests. But these are expensive, labor-intensive, less specific, and benign urinary conditions can compromise their reliability, they added.
A panel like the one used in the study could help clinicians determine the appropriate frequency of follow-up cytology after bladder cancer resection, the investigators said. But they noted that the validation sets were not ideal and that the urine markers should be further explored in a larger, independent cohort.
The National Cancer Institute funded the research. One of the researchers, Dr. Jones, reported having been a consultant and advisory board member of Astex, Lilly, and Zymo. The other authors reported no conflicts of interest.
A DNA methylation marker panel from urine sediments was superior to gold standard tests for predicting recurrence of bladder cancer, investigators reported April 1 in Clinical Cancer Research.
Eighty percent of patients with positive scores on the three-marker panel developed recurrent, biopsy-proven urothelial carcinoma after complete resection of the visible primary tumor (95% confidence interval, 62%-98%), reported Dr. Sheng-Fang Su of University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.
The panel’s positive predictive value far exceeded the values for cytology (35%; 95% CI, 14%-56%) and cytoscopy (15%; 95% CI, 0-31%), the investigators reported (Clin. Cancer Res. 2014 [doi:10.1158/1078-0432.CCR-13-2637]).
The prospective study enrolled 90 patients who had undergone transurethral resection of noninvasive urothelial carcinomas (Tis, Ta, T1; grade low high). Median age of patients was 69 years (range, 41-96). Patients with high-grade Ta/T1 tumors had received intravesical Bacillus Calmette-Guerin vaccine or mitomycin C at their physicians’ discretion.
The investigators performed cytology and extracted DNA from 368 urine and bladder wash specimens collected from patients over a seven-year period. Patients also underwent cytoscopy. The investigators used logistic regression to assess the sensitivity and specificity of various combinations of DNA methylation markers.
The optimal panel included a tumor-specific hypermethylated marker (SOX1), an epigenetic marker (IRAK3), and a field defect-associated hypomethylated marker (L1-MET), the researchers said. The panel’s sensitivity was 80% (95% CI, 60%-96%) and specificity was 97% (95% CI, 91%-100%), they reported. The negative predictive value of the panel (74%) resembled that of cytoscopy (80%) and cytology (76%), they said.
Dr. Su and his associates noted that previous marker tests were more sensitive than cytology, including the FDA-approved NMP-22, ImmunoCyst, and UroVysion tests. But these are expensive, labor-intensive, less specific, and benign urinary conditions can compromise their reliability, they added.
A panel like the one used in the study could help clinicians determine the appropriate frequency of follow-up cytology after bladder cancer resection, the investigators said. But they noted that the validation sets were not ideal and that the urine markers should be further explored in a larger, independent cohort.
The National Cancer Institute funded the research. One of the researchers, Dr. Jones, reported having been a consultant and advisory board member of Astex, Lilly, and Zymo. The other authors reported no conflicts of interest.
FROM CLINICAL CANCER RESEARCH
Major finding: A three-marker DNA methylation panel from urine sediments accurately predicted recurrence after bladder tumor resection in 80% of patients with positive results, vs. 35% for cytology and 15% for cytoscopy.
Data source: A prospective study of cytoscopy, cytology, and levels of DNA methylation markers in 90 patients who had undergone resection for noninvasive urothelial carcinoma.
Disclosures: The National Cancer Institute funded the research. One of the researchers, Dr. Jones, reported having been a consultant and advisory board member of Astex, Lilly, and Zymo. The other authors reported no conflicts of interest.
Delayed response in ipilimumab therapy
Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%.1 In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial.2 CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.
Click on the PDF icon at the top of this introduction to read the full article.
Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%.1 In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial.2 CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.
Click on the PDF icon at the top of this introduction to read the full article.
Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%.1 In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial.2 CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.
Click on the PDF icon at the top of this introduction to read the full article.
Current therapeutic options in hairy cell leukemia
Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder that was initially described as leukemic reticuloendotheliosis. The disease is characterized by monocytopenia, organomegaly, constitutional symptoms, and bone marrow fibrosis. Significant advances have improved the diagnosis and management of HCL over the last 55 years. Although HCL has an indolent course, most patients will require treatment of the disease. Indications to initiate therapy include disease-related symptoms, signs of bone marrow failure, or frequent infections. Asymptomatic patients without cytopenias can be observed without the need for therapeutic interventions. Therapeutic options usually consist of chemotherapy, immunotherapy, biological agents, and surgery.
Click on the PDF icon at the top of this introduction to read the full article.
Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder that was initially described as leukemic reticuloendotheliosis. The disease is characterized by monocytopenia, organomegaly, constitutional symptoms, and bone marrow fibrosis. Significant advances have improved the diagnosis and management of HCL over the last 55 years. Although HCL has an indolent course, most patients will require treatment of the disease. Indications to initiate therapy include disease-related symptoms, signs of bone marrow failure, or frequent infections. Asymptomatic patients without cytopenias can be observed without the need for therapeutic interventions. Therapeutic options usually consist of chemotherapy, immunotherapy, biological agents, and surgery.
Click on the PDF icon at the top of this introduction to read the full article.
Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder that was initially described as leukemic reticuloendotheliosis. The disease is characterized by monocytopenia, organomegaly, constitutional symptoms, and bone marrow fibrosis. Significant advances have improved the diagnosis and management of HCL over the last 55 years. Although HCL has an indolent course, most patients will require treatment of the disease. Indications to initiate therapy include disease-related symptoms, signs of bone marrow failure, or frequent infections. Asymptomatic patients without cytopenias can be observed without the need for therapeutic interventions. Therapeutic options usually consist of chemotherapy, immunotherapy, biological agents, and surgery.
Click on the PDF icon at the top of this introduction to read the full article.
An analysis of the variability of breakthrough pain intensity in patients with cancer
Background The management of breakthrough pain in patients with cancer (BTPc) generally includes an initial titration of breakthrough pain medication to an effective dose, followed by the use of that dose in all subsequent episodes. This strategy presumes that an individual patient has a degree of consistency of pain during repeat episodes; however, that presumption has not been formally assessed.
Objective To examine the variation in pain intensity of BTPc episodes within individual patients and across patients.
Methods Data were pooled from 2 randomized, double-blind, crossover studies that used fentanyl pectin nasal spray (FPNS) vs comparator to relieve BTPc. Eligible patients were adults with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and adequately controlled background pain. The FPNS dose was titrated prior to a double-blind treatment consisting of 10 episodes. Pain intensity was reported on an 11-point numeric scale in which 0 = no pain and 10 = worst possible pain. Inter- and intrapatient variabilities of baseline pain intensity scores per episode were analyzed by analysis of covariance via a mixed-effect model. The influences of demographics and ECOG grade at study entry were assessed.
Results Mean baseline pain intensity score was 7.3 (standard deviation, 1.76; range, 2-10) across 1,399 BTPc episodes in 152 patients. The interpatient variability of baseline pain intensity scores was 75.96%; intrapatient variability was 20.64%. Fixed terms for demographics and ECOG grade did not significantly influence baseline pain intensity score (≤ 5% level).
Limitations This was a post hoc analysis.
Conclusions Baseline pain intensity scores during episodes of BTPc vary widely between patients, but vary little within individual patients; this supports the use of a consistent maintenance dosage of analgesia for BTPc, once it has been titrated to an effective dose.
Funding/Support The study was funded by Archimedes Development Ltd.
*To read the full article, click on the PDF icon at the top of this introduction.
Background The management of breakthrough pain in patients with cancer (BTPc) generally includes an initial titration of breakthrough pain medication to an effective dose, followed by the use of that dose in all subsequent episodes. This strategy presumes that an individual patient has a degree of consistency of pain during repeat episodes; however, that presumption has not been formally assessed.
Objective To examine the variation in pain intensity of BTPc episodes within individual patients and across patients.
Methods Data were pooled from 2 randomized, double-blind, crossover studies that used fentanyl pectin nasal spray (FPNS) vs comparator to relieve BTPc. Eligible patients were adults with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and adequately controlled background pain. The FPNS dose was titrated prior to a double-blind treatment consisting of 10 episodes. Pain intensity was reported on an 11-point numeric scale in which 0 = no pain and 10 = worst possible pain. Inter- and intrapatient variabilities of baseline pain intensity scores per episode were analyzed by analysis of covariance via a mixed-effect model. The influences of demographics and ECOG grade at study entry were assessed.
Results Mean baseline pain intensity score was 7.3 (standard deviation, 1.76; range, 2-10) across 1,399 BTPc episodes in 152 patients. The interpatient variability of baseline pain intensity scores was 75.96%; intrapatient variability was 20.64%. Fixed terms for demographics and ECOG grade did not significantly influence baseline pain intensity score (≤ 5% level).
Limitations This was a post hoc analysis.
Conclusions Baseline pain intensity scores during episodes of BTPc vary widely between patients, but vary little within individual patients; this supports the use of a consistent maintenance dosage of analgesia for BTPc, once it has been titrated to an effective dose.
Funding/Support The study was funded by Archimedes Development Ltd.
*To read the full article, click on the PDF icon at the top of this introduction.
Background The management of breakthrough pain in patients with cancer (BTPc) generally includes an initial titration of breakthrough pain medication to an effective dose, followed by the use of that dose in all subsequent episodes. This strategy presumes that an individual patient has a degree of consistency of pain during repeat episodes; however, that presumption has not been formally assessed.
Objective To examine the variation in pain intensity of BTPc episodes within individual patients and across patients.
Methods Data were pooled from 2 randomized, double-blind, crossover studies that used fentanyl pectin nasal spray (FPNS) vs comparator to relieve BTPc. Eligible patients were adults with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and adequately controlled background pain. The FPNS dose was titrated prior to a double-blind treatment consisting of 10 episodes. Pain intensity was reported on an 11-point numeric scale in which 0 = no pain and 10 = worst possible pain. Inter- and intrapatient variabilities of baseline pain intensity scores per episode were analyzed by analysis of covariance via a mixed-effect model. The influences of demographics and ECOG grade at study entry were assessed.
Results Mean baseline pain intensity score was 7.3 (standard deviation, 1.76; range, 2-10) across 1,399 BTPc episodes in 152 patients. The interpatient variability of baseline pain intensity scores was 75.96%; intrapatient variability was 20.64%. Fixed terms for demographics and ECOG grade did not significantly influence baseline pain intensity score (≤ 5% level).
Limitations This was a post hoc analysis.
Conclusions Baseline pain intensity scores during episodes of BTPc vary widely between patients, but vary little within individual patients; this supports the use of a consistent maintenance dosage of analgesia for BTPc, once it has been titrated to an effective dose.
Funding/Support The study was funded by Archimedes Development Ltd.
*To read the full article, click on the PDF icon at the top of this introduction.
Implementation of an oncology exercise and wellness rehabilitation program to enhance survivorship: the Beaumont Health System experience
We developed a multidisciplinary approach to oncology rehabilitation by setting up a physical therapy screening program in a dedicated multidisciplinary clinic to improve survivorship care in the community oncology setting. In June 2011, an oncology rehabilitation program was launched as part of the overall survivorship program to provide patients with an introduction to cancer services, consultation with multiple clinicians, education about their diagnoses, and recommendation for rehabilitation services during or after treatment. The consultation was in conjunction with specialists at the multidisciplinary clinics that were already established within the organization.
Click on the PDF icon at the top of this introduction to read the full article.
We developed a multidisciplinary approach to oncology rehabilitation by setting up a physical therapy screening program in a dedicated multidisciplinary clinic to improve survivorship care in the community oncology setting. In June 2011, an oncology rehabilitation program was launched as part of the overall survivorship program to provide patients with an introduction to cancer services, consultation with multiple clinicians, education about their diagnoses, and recommendation for rehabilitation services during or after treatment. The consultation was in conjunction with specialists at the multidisciplinary clinics that were already established within the organization.
Click on the PDF icon at the top of this introduction to read the full article.
We developed a multidisciplinary approach to oncology rehabilitation by setting up a physical therapy screening program in a dedicated multidisciplinary clinic to improve survivorship care in the community oncology setting. In June 2011, an oncology rehabilitation program was launched as part of the overall survivorship program to provide patients with an introduction to cancer services, consultation with multiple clinicians, education about their diagnoses, and recommendation for rehabilitation services during or after treatment. The consultation was in conjunction with specialists at the multidisciplinary clinics that were already established within the organization.
Click on the PDF icon at the top of this introduction to read the full article.
Pertuzumab in neoadjuvant treatment of HER2-positive early breast cancer
Pertuzumab injection was granted accelerated approval by the US Food and Drug Administration last fall for use in combination with trastuzumab plus docetaxel for neoadjuvant treatment of patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer (either > 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer.1 The accelerated approval was based on improvement in pathologic complete response (pCR) rate in a phase 2 trial.2,3 Data showing improved event-free survival or overall survival are not yet available. Continued approval for this indication is contingent on demonstration of improvement in disease-free survival in a confirmatory trial.
Click on the PDF icon at the top of this introduction to read the full article.
Pertuzumab injection was granted accelerated approval by the US Food and Drug Administration last fall for use in combination with trastuzumab plus docetaxel for neoadjuvant treatment of patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer (either > 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer.1 The accelerated approval was based on improvement in pathologic complete response (pCR) rate in a phase 2 trial.2,3 Data showing improved event-free survival or overall survival are not yet available. Continued approval for this indication is contingent on demonstration of improvement in disease-free survival in a confirmatory trial.
Click on the PDF icon at the top of this introduction to read the full article.
Pertuzumab injection was granted accelerated approval by the US Food and Drug Administration last fall for use in combination with trastuzumab plus docetaxel for neoadjuvant treatment of patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer (either > 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer.1 The accelerated approval was based on improvement in pathologic complete response (pCR) rate in a phase 2 trial.2,3 Data showing improved event-free survival or overall survival are not yet available. Continued approval for this indication is contingent on demonstration of improvement in disease-free survival in a confirmatory trial.
Click on the PDF icon at the top of this introduction to read the full article.
From our pages to your practice
We have some interesting and insightful articles lined up for you this month, beginning with a Commentary by Samuel and Stone on treating HER2-positive breast cancer and asking whether the era of trastuzumab therapy is over. The Commentary and accompanying Community Translations report explore the use of pertuzumab and trastuzumab together, especially in the neoadjuvant setting. The Cleopatra trial has already shown that combining pertuzumab with trastuzumab plus docetaxel as a first-line treatment for HER2-positive metastatic breast cancer significantly prolonged progression-free survival with no increase in cardiac toxic effects, compared with placebo plus trastuzumab plus docetaxel, so perhaps using pertuzumab and trastuzumab upfront might be equally successful.
Click on the PDF icon at the top of this introduction to read the full article.
We have some interesting and insightful articles lined up for you this month, beginning with a Commentary by Samuel and Stone on treating HER2-positive breast cancer and asking whether the era of trastuzumab therapy is over. The Commentary and accompanying Community Translations report explore the use of pertuzumab and trastuzumab together, especially in the neoadjuvant setting. The Cleopatra trial has already shown that combining pertuzumab with trastuzumab plus docetaxel as a first-line treatment for HER2-positive metastatic breast cancer significantly prolonged progression-free survival with no increase in cardiac toxic effects, compared with placebo plus trastuzumab plus docetaxel, so perhaps using pertuzumab and trastuzumab upfront might be equally successful.
Click on the PDF icon at the top of this introduction to read the full article.
We have some interesting and insightful articles lined up for you this month, beginning with a Commentary by Samuel and Stone on treating HER2-positive breast cancer and asking whether the era of trastuzumab therapy is over. The Commentary and accompanying Community Translations report explore the use of pertuzumab and trastuzumab together, especially in the neoadjuvant setting. The Cleopatra trial has already shown that combining pertuzumab with trastuzumab plus docetaxel as a first-line treatment for HER2-positive metastatic breast cancer significantly prolonged progression-free survival with no increase in cardiac toxic effects, compared with placebo plus trastuzumab plus docetaxel, so perhaps using pertuzumab and trastuzumab upfront might be equally successful.
Click on the PDF icon at the top of this introduction to read the full article.
I-125 brachytherapy for prostate cancer linked to small increase in bladder cancer risk
Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.
But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).
The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.
In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.
Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.
"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.
The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.
Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.
But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).
The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.
In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.
Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.
"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.
The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.
Second primary malignancies affected 10.8% of men who received I-125 brachytherapy as monotherapy for prostate cancer, researchers reported in the April issue of Clinical Oncology.
But only bladder cancer had a small increase in risk in these patients compared with the general population, with the highest risk occurring during the first 4 years of follow-up after implant, said Dr. Ann Henry and her associates at St. James’s University Hospital in Leeds, England (Clin. Oncol. 2014;26:210-5).
The investigators studied 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer from 1995 to 2006 at a single public hospital. Their mean age at treatment was 63 years (interquartile range, 58-68). The researchers defined possible radiation-induced cancers as developing at least 5 years after primary radiotherapy, and with histologies distinct from prostate adenocarcinoma. The median follow-up was 8 years with 487 patients (31%) having 10 years or more.
In all, 170 patients (10.8%) were diagnosed with second primary malignancies at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant, the investigators said. Bladder and rectal cancers were the most common, with 10-year cumulative incidences of 1% and 0.84%, respectively.
Only bladder cancer had a standardized incidence rate that exceeded that of the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46). But the increase was small, and the excess risk was slightly higher during the first 4 years of follow-up (1.69; 95% confidence interval, 0.87-3.34) than during subsequent years (SIR, 1.42; 95% CI, 0.75-2.70). For this reason, the result was probably an artifact of increased urologic surveillance not caused by brachytherapy, said Dr. Henry and her associates.
"This should not act as a deterrent to patients considering low-dose-rate brachytherapy as a treatment modality for early prostate cancer," the investigators said.
The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.
FROM CLINICAL ONCOLOGY
Major Finding: Of 1,805 consecutive patients, 170 (10.8%) had second primary malignancies diagnosed at least 1 year after I-125 brachytherapy implant, and 77 (4.9%) were diagnosed at least 5 years after implant. Only bladder cancer had a standardized incidence rate that was higher than that in the general population (SIR, 1.54; 95% confidence interval, 0.96-2.46).
Data Source: A prospective registry study of 1,805 consecutive patients who received I-125 brachytherapy as monotherapy for localized prostate cancer. Patients were treated from 1995 to 2006 at a single public hospital.
Disclosures: The research was supported by ONCURA, which is part of GE Healthcare. The authors did not disclose any conflicts of interest.
No benefit from androgen deprivation therapy in localized prostate cancer
For most men with localized prostate cancer who defer surgery or radiation, primary androgen deprivation therapy offers no mortality benefit, Dr. Arnold L. Potosky reported.
Dr. Potosky of Georgetown University Medical Center, Washington, D.C., and colleagues looked at 15,170 men with newly diagnosed, clinically localized prostate cancer who did not receive curative therapy, including radiation, radical prostatectomy, or chemotherapy (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.2043]).
Overall, 23% of the cohort had primary androgen deprivation therapy (PADT) initiated within the first year of diagnosis. After adjustment for factors including age, baseline prostate-specific antigen, Gleason score, and T stage, the authors found that there was no difference between PADT-treated men and their PADT-naive counterparts in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.97-1.11) or prostate-cancer specific mortality (HR, 1.03; 95% CI, 0.89-1.19).
Indeed, despite its widespread use among patients who do not undergo curative-intent treatments, "the risk of serious adverse events and the high costs associated with its use mitigate any clinical or policy rationale for PADT use in these men," the authors wrote.
They did report a small but significant decreased risk of all-cause mortality (HR, 0.88; 95% CI, 0.78-0.97) in men with high-risk cancer (pretreatment PSA greater than 20; Gleason score, 8-10; clinical stage, T2c-T3a), but "the observed benefit was relatively small and should not be taken as definitive, given the limitations of our data," they noted.
An increased risk of death was reported in men with low-risk cancer (HR, 1.41; 95% CI, 0.99-1.82) and no difference in risk for men with intermediate-risk cancer (HR, 1.12; 95% CI, 0.92-1.32). There were no differences in risk of prostate cancer mortality by risk group category.
The authors disclosed no conflicts of interest related to this study. The study was supported by grants from the National Cancer Institute.
For most men with localized prostate cancer who defer surgery or radiation, primary androgen deprivation therapy offers no mortality benefit, Dr. Arnold L. Potosky reported.
Dr. Potosky of Georgetown University Medical Center, Washington, D.C., and colleagues looked at 15,170 men with newly diagnosed, clinically localized prostate cancer who did not receive curative therapy, including radiation, radical prostatectomy, or chemotherapy (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.2043]).
Overall, 23% of the cohort had primary androgen deprivation therapy (PADT) initiated within the first year of diagnosis. After adjustment for factors including age, baseline prostate-specific antigen, Gleason score, and T stage, the authors found that there was no difference between PADT-treated men and their PADT-naive counterparts in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.97-1.11) or prostate-cancer specific mortality (HR, 1.03; 95% CI, 0.89-1.19).
Indeed, despite its widespread use among patients who do not undergo curative-intent treatments, "the risk of serious adverse events and the high costs associated with its use mitigate any clinical or policy rationale for PADT use in these men," the authors wrote.
They did report a small but significant decreased risk of all-cause mortality (HR, 0.88; 95% CI, 0.78-0.97) in men with high-risk cancer (pretreatment PSA greater than 20; Gleason score, 8-10; clinical stage, T2c-T3a), but "the observed benefit was relatively small and should not be taken as definitive, given the limitations of our data," they noted.
An increased risk of death was reported in men with low-risk cancer (HR, 1.41; 95% CI, 0.99-1.82) and no difference in risk for men with intermediate-risk cancer (HR, 1.12; 95% CI, 0.92-1.32). There were no differences in risk of prostate cancer mortality by risk group category.
The authors disclosed no conflicts of interest related to this study. The study was supported by grants from the National Cancer Institute.
For most men with localized prostate cancer who defer surgery or radiation, primary androgen deprivation therapy offers no mortality benefit, Dr. Arnold L. Potosky reported.
Dr. Potosky of Georgetown University Medical Center, Washington, D.C., and colleagues looked at 15,170 men with newly diagnosed, clinically localized prostate cancer who did not receive curative therapy, including radiation, radical prostatectomy, or chemotherapy (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.2043]).
Overall, 23% of the cohort had primary androgen deprivation therapy (PADT) initiated within the first year of diagnosis. After adjustment for factors including age, baseline prostate-specific antigen, Gleason score, and T stage, the authors found that there was no difference between PADT-treated men and their PADT-naive counterparts in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.97-1.11) or prostate-cancer specific mortality (HR, 1.03; 95% CI, 0.89-1.19).
Indeed, despite its widespread use among patients who do not undergo curative-intent treatments, "the risk of serious adverse events and the high costs associated with its use mitigate any clinical or policy rationale for PADT use in these men," the authors wrote.
They did report a small but significant decreased risk of all-cause mortality (HR, 0.88; 95% CI, 0.78-0.97) in men with high-risk cancer (pretreatment PSA greater than 20; Gleason score, 8-10; clinical stage, T2c-T3a), but "the observed benefit was relatively small and should not be taken as definitive, given the limitations of our data," they noted.
An increased risk of death was reported in men with low-risk cancer (HR, 1.41; 95% CI, 0.99-1.82) and no difference in risk for men with intermediate-risk cancer (HR, 1.12; 95% CI, 0.92-1.32). There were no differences in risk of prostate cancer mortality by risk group category.
The authors disclosed no conflicts of interest related to this study. The study was supported by grants from the National Cancer Institute.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Major finding: Men with localized prostate cancer who deferred curative treatment but opted for primary androgen deprivation therapy saw no significant decrease in mortality (hazard ratio, 0.97; 95% confidence interval, 0.97-1.11).
Data source: A retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans (n = 15,170).
Disclosures: The authors disclosed no conflicts of interest related to this study. The study was supported by grants from the National Cancer Institute.