title: Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a phase I study.
abstract: The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24-79) years, World Health Organisation performance status 0-2 and median four marker lesions, received irinotecan 180 mg m(-2) on day 1, oxaliplatin 85-100 mg m(-2) on day 15 and UFT 200-300 mg m(-2) day(-1) with LV 90 mg day(-1), days 1-21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT 300 mg m(-2) day(-1)), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT 250 mg m(-2) day(-1)). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180 mg m(-2) on day 1, oxaliplatin 100 mg m(-2) on day 15 and UFT 250 mg m(-2) day(-1) with LV 90 mg day(-1) on days 1-21 of a 28-day cycle for future studies.
authors.affiliation: Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester M20 4BX, UK.
authors.forename: H Y
authors.initials: HY
authors.lastname: Sheikh
authors.forename: J W
authors.initials: JW
authors.lastname: Valle
authors.forename: K
authors.initials: K
authors.lastname: Palmer
authors.forename: A
authors.initials: A
authors.lastname: Sjursen
authors.forename: O
authors.initials: O
authors.lastname: Craven
authors.forename: G
authors.initials: G
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Swindell
authors.forename: M P
authors.initials: MP
authors.lastname: Saunders
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005641:Tegafur; D014498:Uracil; D000077146:Irinotecan; D002955:Leucovorin; D002166:Camptothecin