NEW YORK (Reuters Health) Mar 23 - Capecitabine plus oxaliplatin should be considered a standard-of-care for adjuvant therapy following stage III colon cancer resection, according to a new study.
The combination, often called XELOX or CAPOX, was previously used for stage IV metastatic disease. However in a head-to-head comparison with a standard bolus fluorouracil (FU) and folinic acid (FA) adjuvant regimen, XELOX improved 3-year disease-free survival for patients with stage III disease.
The study was published online March 7 in the Journal of Clinical Oncology.
"Capecitabine plus oxaliplatin can now be considered a standard of care -- not the standard of care," said Dr. Michael O'Connell, the associate chairman of the National Surgical Adjuvant Breast and Bowel Project, a U.S. colorectal cancer research group.
Dr. James Cassidy, head of Medical Oncology at the University of Glasgow in Scotland, agreed that the study should simply add to oncologists' armamentarium, not completely replace FU/FA regimens, which have been standard since the late 1990s.
"XELOX already is our standard in this situation and I think it should be a standard," Dr. Cassidy told Reuters Health in an email. "I don't really think one has to get down to just one standard. I believe there are good reasons for us to be able to choose between regimens for individual patients."
He added that about 50% of stage III colon cancer patients already receive a XELOX regimen in the United Kingdom, based on enrollment in a current trial that Dr. Cassidy is participating in.
In the U.S. study, patients with locally advanced, node-positive colon cancer were randomized to receive either a standard bolus, FA/FU adjuvant regimen (n=942) or a capecitabine plus oxaliplatin regimen (n=944) within 8 weeks of surgical resection.
The FA/FU treatment regimens were either the Mayo Clinic (n=664; 24 weeks, 6 cycles) or Roswell Park (278; 32 weeks, 4 cycles) standard protocols. Patients in the capecitabine plus oxaliplatin, or XELOX, arm received a 2-hour intravenous infusion of oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle for eight cycles.
Disease-free survival was the main outcome measure in the study, and patients were followed for a median duration of 55 months.
When enrollment was closed, 31.3% of patients in the XELOX group had relapsed, developed a new colon cancer, or died, compared with 37.5% of the FU/FA group.
In terms of disease-free survival, patients taking XELOX also had a 20% reduction in relative risk (HR 0.80; P=.0045).
Four- and five-year disease-free-survival rates were also better in the XELOX group (68.5% vs. 62.3% and 66.1% vs. 59.8%, respectively), "demonstrating that superior efficacy of XELOX versus FU/FA was maintained over time," the investigators, led by Dr. Daniel Haller at the University of Pennsylvania, write.
Capecitabine, which is given orally, is potentially more convenient to administer than intravenous FU-based regimens. However, the cheaper costs of oral chemotherapy could be outweighed by an increase in adverse events found in the XELOX group.
"A central venous catheter is sometimes required for the administration of oxaliplatin anyway, and management of the increased toxicity with (capecitabine plus oxaliplatin) also costs money," said Dr. O'Connell.
In the study, 55% of patients in the XELOX group suffered a grade 3/4 adverse event, compared with 47% of patients in the FU/FA group (P<.05). Neurosensory toxicity was also far more common in the XELOX group, with 78% of patients reporting some level of neurotoxicity versus 8% in the FU/FA group.
Dr. Cassidy said the adverse events reported with XELOX in the trial were acceptable, but that "some oncologists still feel it's a bit more toxic in everyday usage -- particularly with respect to diarrhea."
Another barrier, he added, is that physicians may be paid less for switching to an oral-based regimen. "In some countries the clinician or institution gets a payment for IV drug administration but gets much less -- sometimes nothing -- for prescription of an oral drug. So there can be perverse incentives for sticking with an all-IV regimen," he said.
The study was supported by F. Hoffman-La Roche, and several of the authors report financial ties with companies that include Merck, Roche, Hoffman-La Roche and AstraZeneca.
SOURCE: http://bit.ly/ec5nwk
J Clin Oncol 2011.
The combination, often called XELOX or CAPOX, was previously used for stage IV metastatic disease. However in a head-to-head comparison with a standard bolus fluorouracil (FU) and folinic acid (FA) adjuvant regimen, XELOX improved 3-year disease-free survival for patients with stage III disease.
The study was published online March 7 in the Journal of Clinical Oncology.
"Capecitabine plus oxaliplatin can now be considered a standard of care -- not the standard of care," said Dr. Michael O'Connell, the associate chairman of the National Surgical Adjuvant Breast and Bowel Project, a U.S. colorectal cancer research group.
Dr. James Cassidy, head of Medical Oncology at the University of Glasgow in Scotland, agreed that the study should simply add to oncologists' armamentarium, not completely replace FU/FA regimens, which have been standard since the late 1990s.
"XELOX already is our standard in this situation and I think it should be a standard," Dr. Cassidy told Reuters Health in an email. "I don't really think one has to get down to just one standard. I believe there are good reasons for us to be able to choose between regimens for individual patients."
He added that about 50% of stage III colon cancer patients already receive a XELOX regimen in the United Kingdom, based on enrollment in a current trial that Dr. Cassidy is participating in.
In the U.S. study, patients with locally advanced, node-positive colon cancer were randomized to receive either a standard bolus, FA/FU adjuvant regimen (n=942) or a capecitabine plus oxaliplatin regimen (n=944) within 8 weeks of surgical resection.
The FA/FU treatment regimens were either the Mayo Clinic (n=664; 24 weeks, 6 cycles) or Roswell Park (278; 32 weeks, 4 cycles) standard protocols. Patients in the capecitabine plus oxaliplatin, or XELOX, arm received a 2-hour intravenous infusion of oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle for eight cycles.
Disease-free survival was the main outcome measure in the study, and patients were followed for a median duration of 55 months.
When enrollment was closed, 31.3% of patients in the XELOX group had relapsed, developed a new colon cancer, or died, compared with 37.5% of the FU/FA group.
In terms of disease-free survival, patients taking XELOX also had a 20% reduction in relative risk (HR 0.80; P=.0045).
Four- and five-year disease-free-survival rates were also better in the XELOX group (68.5% vs. 62.3% and 66.1% vs. 59.8%, respectively), "demonstrating that superior efficacy of XELOX versus FU/FA was maintained over time," the investigators, led by Dr. Daniel Haller at the University of Pennsylvania, write.
Capecitabine, which is given orally, is potentially more convenient to administer than intravenous FU-based regimens. However, the cheaper costs of oral chemotherapy could be outweighed by an increase in adverse events found in the XELOX group.
"A central venous catheter is sometimes required for the administration of oxaliplatin anyway, and management of the increased toxicity with (capecitabine plus oxaliplatin) also costs money," said Dr. O'Connell.
In the study, 55% of patients in the XELOX group suffered a grade 3/4 adverse event, compared with 47% of patients in the FU/FA group (P<.05). Neurosensory toxicity was also far more common in the XELOX group, with 78% of patients reporting some level of neurotoxicity versus 8% in the FU/FA group.
Dr. Cassidy said the adverse events reported with XELOX in the trial were acceptable, but that "some oncologists still feel it's a bit more toxic in everyday usage -- particularly with respect to diarrhea."
Another barrier, he added, is that physicians may be paid less for switching to an oral-based regimen. "In some countries the clinician or institution gets a payment for IV drug administration but gets much less -- sometimes nothing -- for prescription of an oral drug. So there can be perverse incentives for sticking with an all-IV regimen," he said.
The study was supported by F. Hoffman-La Roche, and several of the authors report financial ties with companies that include Merck, Roche, Hoffman-La Roche and AstraZeneca.
SOURCE: http://bit.ly/ec5nwk
J Clin Oncol 2011.
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