5-FU/Leucovorin Plus Oxaliplatin Significantly Improves Disease- Free Survival in Colorectal Ca Pts

ORLANDO-The addition of oxaliplatin(Drug information on oxaliplatin) (Eloxatin) to weekly bolus fluorouracil(Drug information on fluorouracil)/leucovorin (5-FU/LV) significantly improves 3-year diseasefree survival in patients with stage II and III colon cancer, according to Norman Wolmark, MD, of Allegheny General Hospital in Pittsburgh. Dr. Wolmark presented the results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) study C-07 (abstract 3500). The 3-year disease free-survival rate was 71.6% for those patients receiving 5-FU/LV alone and 76.5% for those receiving 5-FU/LV plus oxaliplatin (FLOX). "This translates into an overall 21% risk reduction," Dr. Wolmark reported. Disease-free survival was the primary study endpoint. "The data confirm and extend the results of the MOSAIC trial," Dr. Wolmark said. The MOSAIC (Multicenter International Study of Oxaliplatin/ FU-LV in the Adjuvant Treatment of Colon Cancer) trial has a 3-year disease- free survival rate of 77.9% and was updated at ASCO 2005 by Aimery de Gramont, MD (see page 5). In a press conference earlier at the ASCO meeting, Dr. Wolmark said the results of the C-07 trial were "superimposable" on the MOSAIC trial and that patients should not be denied the benefits of oxaliplatin. In comments after the press conference, he said that he was optimistic that the 3-year results for C-07 would translate into 5- year results. Neurotoxicity Most Troubling "The overall toxicity was greater for the FLOX arm, but not that much greater," Dr. Wolmark reported. Grade 0 to 2 toxicities occurred in 49% of the 5-FU/LV arm and in 38% of the FLOX arm, but grade 3 toxicities were higher in the FLOX arm (50% vs 41% in the 5-FU/LV arm; Table 1). "The most troubling toxicity related to oxaliplatin was neurotoxicity," Dr. Wolmark said. In the FLOX arm, 85.4% of patients had some degree of neurotoxicty during treatment, although this rate dropped to 29.4% of patients at 12 months after treatment stopped. Grade 3 neurotoxicity occurred in 8.5% of patients in the FLOX arm during treatment and 0.5% of patients at 12 months after treatment stopped. These percentages for neurotoxicity were lower in the C-07 study than in the MOSAIC trial, "perhaps because we used a lower cumulative dose of oxaliplatin," Dr. Wolmark said. The C-07 trial protocol stipulated a cumulative dose of 765 mg/m² and the MOSAIC trial, 1,020 mg/m². Overall, 73% of patients in the C-07 trial received the protocol-stipulated dose. "The only unanticipated toxicity that we saw was a form of transmural enterocolitis requiring hospitalization and rehydration," Dr. Wolmark reported. This event occurred in 34 patients (2.7%) in the 5-FU/LV arm and in 56 patients (4.5%) in the FLOX arm. There were 14 deaths in the 5-FU/ LV arm and 15 deaths in the FLOX arm. 'Monotonously Well Distributed' Patient Characteristics Patients with stage II (28.6%) or stage III colon cancer were randomized to receive either 5-FU/LV (5-FU: 500 mg/m² IV bolus weekly; leucovorin: 500 mg/m² IV weekly for 6 weeks of the 8-week cycle, repeated three times) or FLOX (the same 5-FU/LV regimen plus oxaliplatin [85 mg/m² IV] on weeks 1, 3, and 6 of each 8-week cycle, repeated three times). "The data support the use of weekly bolus 5-FU/LV in combination with oxaliplatin in adjuvant colon cancer," Dr. Wolmark concluded. "Patient characteristics were monotonously well distributed for sex, age, tumor location, and above all number of nodes, which was not par- ticularly surprising since the trial was stratified based on the number of positive nodes," Dr. Wolmark said. About 29% of patients in both arms had no positive nodes, 45% had one to three positive nodes, and 25% had more than three positive nodes. Slightly more than half of the patients in each arm were < 60 years old.