title: Phase II study of a triplet regimen in advanced colorectal cancer using methotrexate, oxaliplatin and 5-fluorouracil.
abstract: Building upon the concept of schedule-specific biochemical modulation of 5-fluorouracil (FU), which alternates bolus and continuous infusion (CI) FU, we have incorporated oxaliplatin (l-OHP) following the bolus part of the regimen to explore the activity of this new combination. Patients with advanced, untreated, measurable colorectal cancer received sequential methotrexate (MTX) (days 1 and 15)-->l-OHP+FU (days 2 and 16) (200, 85 and 600 mg m(-2), respectively) followed by 3 weeks of CI FU (200 mg m(-2) day(-1)) given from day 29 to 50, modulated by weekly leucovorin (LV) (20 mg m(-2)). After 1 week of rest, the second cycle was started. The treatment was continued until progression or patient's refusal. According to the intention-to-treat analysis on all 46 patients accrued, the response rate was 42% (95% CL=28-55%), with three complete responses and 16 partial responses. The median overall survival was 15.9 months and the median progression-free survival 6.9 months. Toxicity was very mild, with the bolus part of the regimen more toxic than the infusional part (24 vs 7% of grade III-IV, respectively). This new combination of MTX -->l-OHP-FU followed by FU CI is well tolerated, feasible and produces activity results similar to other more simple, but more toxic, regimens. Pros and cons of the different fluoropyrimidines-l-OHP combinations are discussed.
authors.affiliation: Medical Oncology, Ospedale San Martino, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Guglielmi
authors.forename: S
authors.initials: S
authors.lastname: Barni
authors.forename: A
authors.initials: A
authors.lastname: Zaniboni
authors.forename: N
authors.initials: N
authors.lastname: Pella
authors.forename: O
authors.initials: O
authors.lastname: Belvedere
authors.forename: G D
authors.initials: GD
authors.lastname: Beretta
authors.forename: F
authors.initials: F
authors.lastname: Grossi
authors.forename: L
authors.initials: L
authors.lastname: Frontini
authors.forename: F
authors.initials: F
authors.lastname: Puglisi
authors.forename: R
authors.initials: R
authors.lastname: Labianca
authors.forename: A
authors.initials: A
authors.lastname: Sobrero
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil; D008727:Methotrexate