title: Adjuvant sequential methotrexate --> 5-fluorouracil vs 5-fluorouracil plus leucovorin in radically resected stage III and high-risk stage II colon cancer.
abstract: 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 x 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.
authors.affiliation: Oncologia Medica Ospedale S Martino, Largo Benzi 10, Genova 16132, Italy. alberto.sobrero@hsanmartino.liguria.it
authors.forename: A
authors.initials: A
authors.lastname: Sobrero
authors.forename: G
authors.initials: G
authors.lastname: Frassineti
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: L
authors.initials: L
authors.lastname: Dogliotti
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: F
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: F D
authors.initials: FD
authors.lastname: Costanzo
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015996:Survival Rate
chemical_list: D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate