PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)-leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m(2)/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m(2), as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU-LV occurred in </= 5% of the patients (</= 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU-LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P <. 001). The median progression-free survival time was 6.1 months with 5-FU-LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU-LV (P =.048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU-LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.
RCT Entities:
PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)-leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m(2)/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m(2), as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU-LV occurred in </= 5% of the patients (</= 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU-LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P <. 001). The median progression-free survival time was 6.1 months with 5-FU-LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU-LV (P =.048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU-LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.
Authors: Wendy L Allen; Richard C Turkington; Leanne Stevenson; Gail Carson; Vicky M Coyle; Suzanne Hector; Philip Dunne; Sandra Van Schaeybroeck; Daniel B Longley; Patrick G Johnston Journal: Mol Cancer Ther Date: 2012-06-04 Impact factor: 6.261
Authors: Eduardo de Santibañes; Diego Fernandez; Carlos Vaccaro; Guillermo Ojea Quintana; Fernando Bonadeo; Juan Pekolj; Carlos Bonofiglio; Ernesto Molmenti Journal: World J Surg Date: 2010-09 Impact factor: 3.352
Authors: René Adam; Gerard Pascal; Denis Castaing; Daniel Azoulay; Valerie Delvart; Bernard Paule; Francis Levi; Henri Bismuth Journal: Ann Surg Date: 2004-12 Impact factor: 12.969