A phase I-II study of 14-days continuous infusion of 5-fluorouracil with weekly bolus leucovorin in metastatic colorectal carcinoma.
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.
Sinnige
H A
HA
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Nanninga
A G
AG
Verschueren
R C
RC
Sleijfer
D T
DT
de Vries
G E
GE
Willemse
P H
PH
Mulder
N H
NH
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
D002955:Leucovorin; D005472:Fluorouracil