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

• Published in: Journal of clinical oncology Vol. 19; no. 22; pp. 4195 - 4201
• Main Authors: BECOUARN, Yves, GAMELIN, Erick, BEKRADDA, Mohamed, MIGNARD, Dominique, MOUSSEAU, Mireille, COUDERT, Bruno, NEGRIER, Sylvie, PIERGA, Jean-Yves, RAOUL, Jean-Luc, PROVENCAL, Jocelyne, RIXE, Olivier, KRISCH, Claude, GERMA, Caroline
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15-11-2001; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Chemotherapy; Chemotherapy, Adjuvant; Colonic Neoplasms - drug therapy; Colonic Neoplasms - mortality; Colonic Neoplasms - secondary; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Humans; Leucovorin - administration & dosage; Male; Medical sciences; Middle Aged; Organoplatinum Compounds - administration & dosage; Pharmacology. Drug treatments; Rectal Neoplasms - drug therapy; Rectal Neoplasms - mortality; Rectal Neoplasms - secondary; Survival Rate; Treatment Outcome; Antineoplastic agent; Rectal disease; Multicenter study; Randomization; Isomerases; Oxaliplatin; Phase II trial; Intestinal disease; Colon; Platinum II Complexes; Fluorouracil; Human; Enzyme; Treatment efficiency; Fluoropyrimidine derivatives; DNA topoisomerase; Enzyme inhibitor; Malignant tumor; Colonic disease; Irinotecan; Chemotherapy; Rectum; Digestive diseases; Pyrimidine derivatives; Metastatic
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2001.19.22.4195

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.
Sixty-two patients were treated: arm FC/FO (32 patients) 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 and 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) received oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) every 3 weeks.
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.
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.