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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

From the Institut Bergonié, Bordeaux; Centre Paul Papin, Angers; Centre Georges-François Leclerc, Dijon; Centre Léon Bérard, Lyon; Institut Curie and Aventis, Paris; Centre Eugène Marquis, Rennes; Centre Hospitalo-Universitaire, Grenoble; Clinique C. Bernard, Metz; Centre Hospitalo-Universitaire, Amiens; and Cvitkovic et Associés Consultants, Kremlin-Bicêtre, France.

Address reprint requests to Yves Bécouarn, MD, Department of Digestive Oncology, Institut Bergonié, Regional Cancer Center, 229, cours de l’Argonne, 33076 Bordeaux Cedex, France; email: becouarn{at}bergonie.org

PURPOSE: To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating 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 patients) received, every 4 weeks, FA 200 mg/m² followed by a 400-mg/m² 5-FU bolus injection, then a 600-mg/m² continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m² on day 1) and oxaliplatin (85 mg/m² on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m² and irinotecan 200 mg/m² 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 bitherapy 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, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-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 tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.

Presented in part at the Thirty-Sixth Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, May 19-23, 2000.

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