A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: Results of NSABP Protocol C-07

Authors: N. Wolmark, H. S. Wieand, J. P. Kuebler, L. Colangelo, R. E. Smith


Background: The primary aim of this two-arm randomized prospective study was to determine whether FULV + oxaliplatin (FLOX) would prolong 3-year disease-free survival (DFS) compared to FULV.

Methods: Between February 2000 and November 2002, 2,407 patients with follow-up (1207 and 1200 in the respective arms) with stage II (28.6%) or III carcinoma of the colon were randomized to receive either FULV (5-FU, 500 mg/m2 iv bolus weekly x 6; LV, 500 mg/m2 iv weekly x 6, each 8 week cycle x 3) or FLOX (same FULV regimen with oxaliplatin 85 mg/m2 iv administered on weeks 1, 3, and 5 of each 8 week cycle x 3). The primary end point was DFS. Events were defined as first recurrence, second primary cancer, or death.

Results: The median follow-up for patients who were still alive was 34 months. The hazard rate (FLOX vs. FULV) was 0.79 with 95% CI (0.67, 0.93), a 21% risk reduction in favor of FLOX. (See table below.) Grade 3 NCI-Sanofi neurosensory toxicity was noted in 8% of patients on FLOX and 1% of those receiving FULV. Hospitalization for diarrhea or dehydration associated with bowel wall thickening occurred in 56 patients on FLOX and 34 patients on FULV. There were 14 and 15 deaths while patients were on treatment for FULV and FLOX, respectively.

Conclusions: The addition of oxaliplatin to weekly FULV significantly improved 3-year DFS in patients with Stage II and III colon cancer. Supported by Public Health Service grants U10-CA-12027 and U10-CA-69651 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. N. Wolmark and J. P. Kuebler have served on advisory boards and have received honoraria from Sanofi-Synthelabo, Inc.

	N	Events	3yr % DFS
FULV	1207	332	71.6
FLOX	1200	272	76.5

　　P = 0.004