Phase I trial of 5-fluorouracil by 24-hour infusion weekly.

Abstract:

:A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorouracil as a single agent on this schedule, we treated 26 patients at doses ranging from 2800 to 3400 mg/m2 per week. Two-thirds of the patients had failed previous therapy, and most were symptomatic from their disease. Over half of the patients had metastatic colorectal cancer. The dose-limiting toxicity was diarrhea: Grade 3 or 4 toxicity occurred at every level tested. Twenty-two of the 26 patients required therapy interruption because of toxicity. The severity of this toxicity indicated that escalation of 5-fluorouracil on this schedule beyond the 2600 mg/m2 known to be tolerated in the PALA-containing regimen, would be impractical. Two patients, both with previously untreated colorectal cancer, had partial remissions lasting three and five months respectively. This dose-intense schedule of 5-fluorouracil administration will be explored further in large-scale randomized trials.

journal_name

Invest New Drugs

authors

Haas NB,Hines JB,Hudes GR,Johnston N,Ozols RF,O'Dwyer PJ

doi

10.1007/BF00874152

subject

Has Abstract

pub_date

1993-05-01 00:00:00

pages

181-5

issue

2-3

eissn

0167-6997

issn

1573-0646

journal_volume

11

pub_type

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