ROCHESTER, Minnesota—An interim analysis of the North American Intergroup Study N9741 suggests that oxaliplatin(Drug information on oxaliplatin) (Eloxatin, investigational in the United States) plus infusional fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin (FOLFOX) may be the new standard of care for patients with metastatic colorectal cancer.
"Treatment with FOLFOX resulted in significantly increased time to progression, overall survival, and response rate when compared to irinotecan(Drug information on irinotecan) (CPT-11, Camptosar)/bolus 5-FU/leucovorin (IFL)," Richard M. Goldberg, MD, professor of oncology, Mayo Medical School, said at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 511). "The toxicity profile favors FOLFOX over IFL," he added.
The primary goal of the study was to compare times to tumor progression. The trial, which at one time had six different arms, underwent several modifications: In March 1999 to include oxaliplatin; in March 2000, when IFL became the standard of care; and in April 2001 to address IFL toxicity, which led to a dose reduction in the IFL arm. However, the findings reported at ASCO include results only from the 765 patients enrolled in the three final arms prior to lowering the IFL dose. The three regimens were as follows:
- IFL (Saltz regimen): irinotecan 125 mg/m² plus leucovorin 20 mg/m² and bolus 5-FU 500 mg/m² on days 1, 8, 15, and 22 every 6 weeks
- FOLFOX4 (de Gramont regimen): oxaliplatin 85 mg/m² on day 1, followed by leucovorin 200 mg/m² and a loading dose of 5-FU at 400 mg/m². The loading dose is followed by a 22-hour infusion of 5-FU at 600 mg/m². The 5-FU and leucovorin are repeated on days 1 and 2 every 2 weeks.
- IROX (Wasserman regimen): oxaliplatin 85 mg/m² plus irinotecan 200 mg/m² on day 1 every 3 weeks.
A planned interim intent-to-treat analysis was conducted in April 2002, because 81% of the planned events had occurred, and upon review, the North Central Cancer Treatment Group data monitoring committee recommended the study’s release. "The stopping boundaries for the comparison of IFL and FOLFOX were crossed," Dr. Goldberg said.
The median age of the 795 patients was 61 years; 94% to 95% had an ECOG performance score of 0 to 1, and 15% to 16% had received prior adjuvant therapy. At the time of this analysis, the median follow-up for living patients was 12 months, and approximately 70% of patients had shown disease progression.
The median time to progression was 6.9 months for IFL, 8.8 months for FOLFOX4, and 6.7 months for irinotecan plus oxaliplatin (see table below). "The time to progression curves for IFL and FOLFOX diverged early, and this separation was maintained until 2 years from study entry," Dr. Goldberg said.
Median overall survival with IFL was 14.1 months, with FOLFOX 18.6 months, and with IROX 16.5 months, Dr. Goldberg said. "One year after they had been enrolled on the study, 58%, 71%, and 65% of patients were alive, respectively." The response rates were IFL 29%, FOLFOX 38%, and IROX 28%.
