title: A phase I-II study of 14-days continuous infusion of 5-fluorouracil with weekly bolus leucovorin in metastatic colorectal carcinoma.
abstract: A consecutive phase I and phase II study of a 14-days continuous infusion schedule of 5-fluorouracil with weekly bolus injection leucovorin was performed in 10 and 21 patients, respectively. Chemotherapy courses were repeated every 4 weeks. 1 patient in the phase I study was pretreated, all the others had no prior chemotherapy. 300 mg/m2 continuous infusion of 5-fluorouracil for 14 days could not be combined with any dose of leucovorin 20-200 mg/m2 without severe toxicity, mainly gastrointestinal. A 5-fluorouracil dose of 200 mg/m2 day for 2 weeks, combined with weekly bolus injection of 200 mg/m2 leucovorin was found to be feasible. The phase II study was performed at this dose level. In 21 patients a response rate of 5/21 [23.8%, 95% confidence interval (CI) 8.2-47.1%] was observed, and the overall response rate was 8/29 (27.6%, 95% CI 12.7-47.2%). Responses were observed in patients with liver (4), lung (1), abdominal (1), and multiple (2) metastases. Median survival was 14.5 months. Toxicity was low, mucositis WHO grade 1-2 being most frequent (36/113 courses = 31.9%). Patients' acceptance of this continuous infusion schedule was generally good.
authors.affiliation: Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Sinnige
authors.forename: A G
authors.initials: AG
authors.lastname: Nanninga
authors.forename: R C
authors.initials: RC
authors.lastname: Verschueren
authors.forename: D T
authors.initials: DT
authors.lastname: Sleijfer
authors.forename: G E
authors.initials: GE
authors.lastname: de Vries
authors.forename: P H
authors.initials: PH
authors.lastname: Willemse
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D002955:Leucovorin; D005472:Fluorouracil