Randomized multicenter phase II study comparing a combination of fluorouracil and folinic acid and alternating irinotecan and oxaliplatin with oxaliplatin and irinotecan in fluorouracil-pretreated metastatic colorectal cancer patients

Purpose : To assess antitumor activity and safety of two regimens in advanc ed colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resista nce in a randomized phase II study: 5-FU/folinic acid (FA) combined with al ternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy ), and an oxaliplatin/irinotecan (OC) combination. Patients and Methods: Sixty-two patients were treated: arm FC/FO (32 patien ts) received, every 4 weeks, FA 200 mg/m(2) followed by a 400-mg/m(2) 5-FU bolus injection, then a 600-mg/m(2) continuous infusion of 5-FU on days 1 a nd 2 every 2 weeks administered alternately with irinotecan (180 mg/m(2) on day 1) and oxaliplatin (85 mg/m(2) on day 15). Arm OC (30 patients) receiv ed oxaliplatin 85 Mg/M2 and irinotecan 200 mg/m(2) every 3 weeks. Results: In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bi therapy regimen. Median progression-free and overall survival times were 8. 2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, r espectively, in the OC arm. Main grade 3/4 toxicities were, respectively, n eutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatm ent-related deaths occurred. Conclusion: The every-3-weeks OC combination is safe and active in advanced 5-FU-resistant CRC patients. The lower activity data seen with the trither apy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule. (C) 2001 by American Society of Clinical Onco logy.