Phase I trial of 5-fluorouracil by 24-hour infusion weekly.
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.
Haas
N B
NB
Fox Chase Cancer Center, Philadelphia, PA.
Hines
J B
JB
Hudes
G R
GR
Johnston
N
N
Ozols
R F
RF
O'Dwyer
P J
PJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D010865:Pilot Projects
D005472:Fluorouracil