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Haas NB , Hines JB , Hudes GR , Johnston N , Ozols RF , O'Dwyer PJ
Phase I trial of 5-fluorouracil by 24-hour infusion weekly
Investigational New Drugs. 1993 ;11(2-3) :181-185
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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.
Notes
01676997 (ISSN) Cited By: 7; Export Date: 31 May 2006; Source: Scopus CODEN: INNDD Language of Original Document: English Correspondence Address: Haas, N.B.; Department of Medical Oncology; Fox Chase Cancer Center; 7701 Burholme Avenue Philadelphia, PA 19111, United States Chemicals/CAS: fluorouracil, 51-21-8; sparfosic acid, 51321-79-0, Fluorouracil, 51-21-8