ORLANDOA phase III clinical trial of first-line therapy in advanced
colorectal cancer showed improved progression-free survival (PFS) for weekly
infusional FUFOXfluorouracil/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 drugsoxaliplatin,
irinote-can (CPT-11, Camptosar), and 5-FU/FA)available to all patients, Dr.
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 or
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).