Adjuvant sequential methotrexate?5-fluorouracil vs 5-fluorouracil plus leucovorin in radically resected stage III and high-risk stage II colon cancer.

The aim of the study was to determine whether modulation of 5-fluorouracil (FU) by methotrexate (MTX) improves survival compared to FU+6-s-leucovorin (LV) following potentially curative resection of stage II and III colon cancer. Within 8 weeks from surgery, 1945 patients with stage III (44%) or high-risk stage II (55%) colon cancer were randomly assigned to receive either 6 monthly cycles of FU 370?mg?m^-2 i.v. bolus preceded by LV 100?mg?m^-2 i.v. bolus on days 1-5, or 6 monthly cycles of sequential MTX 200?mg?m^-2 i.v. days 1 and 15 and FU 600?mg?m^-2 i.v. on days 2 and 16 followed by LV rescue (15?mg given p.o. q 6?h×6 doses). Levamisole 50?mg p.o. t.i.d. on days 1-3, every 14 days for 6 months, was planned to be given in both arms. After a median follow-up of 4.2 years, 568 patients have relapsed and 403 have died. Survival was similar with MTX?FU and FU+LV (77 vs 77%at 5 years; P=0.90), as were 5-year disease-free survivals (67 vs 63%; P=0.44). Efficacy results were similar for both stage III and II patients. There were two toxic deaths, two in the MTX?FU arm (0.2%) and zero in the control arm. We conclude that biochemical modulation of FU with LV or with MTX produces similar results in the adjuvant setting of colon cancer.British Journal of Cancer (2005) 92, 24-29. doi:10.1038/sj.bjc.6602276 www.bjcancer.com Published online 21 December 2004 [ABSTRACT FROM AUTHOR]