ORLANDO—A phase III clinical trial of first-line therapy in advanced colorectal cancer showed improved progression-free survival (PFS) for weekly infusional FUFOX—fluorouracil/folinic acid (5-FU/FA)/oxaliplatin (Eloxatin)—compared with the Mayo bolus 5-FU/FA (leucovorin in the United States) regimen, Axel Grothey, MD, University of Halle, Halle, Germany, said at the American Society of Clinical Oncology 38th Annual Meeting (abstract 512).
The fact that salvage therapies appeared to contribute to the long median survival seen in both arms supports making all active drugs—oxaliplatin, irinote-can (CPT-11, Camptosar), and 5-FU/FA)—available to all patients, Dr. Grothey said.
Dr. Grothey noted that at the time the FUFOX study was designed, the Mayo bolus 5-FU/FA regimen was the standard treatment for advanced colorectal cancer. Combination protocols with 5-FU/FA plus either irinotecan(Drug information on irinotecan) or oxaliplatin(Drug information on oxaliplatin) were showing high clinical activity, and infusional 5-FU/FA as a first-line therapy was demonstrating increased response rates and slightly prolonged progression-free survival, but with no effect on overall survival.
Because randomized trials comparing infusional 5-FU/FA plus oxaliplatin with the standard Mayo clinic protocol had not been conducted, Dr. Grothey and his colleagues embarked on the current trial.
The trial included 252 advanced colo-rectal cancer patients treated at 60 centers, randomized to FUFOX (n=123, oxaliplatin 50 mg/m2 2-hour infusion, 5-FU 2,000 mg/m2 24-hour infusion, FA 500 mg/m2, on days 1, 8, 15, and 22 every 5 weeks) or the standard Mayo regimen (n=129, 5-FU bolus 425 mg/m2, FA 20 mg/m2, on days 1 to 5 every 4 weeks).
Among FUFOX patients, 15.4% had received prior adjuvant chemotherapy, compared with 24.8% in the Mayo arm (P = .084). Ten patients withdrew prior to therapy and another four prior to completion of a full cycle, leaving 242 for the safety evaluation and 238 for the efficacy evaluation. The primary endpoint was progression-free survival.
Progression-free survival (intent-to-treat) was 7.8 months for FUFOX, compared with 5.3 months for the Mayo regimen (P = .0001). Early progressive disease in the Mayo group accounted for an early separation of curves favoring the FUFOX regimen. At median follow-up of 32.5 months, overall survival among patients evaluable for efficacy was 16.1 months for the Mayo group and 21.4 months for FUFOX (not significant).
