Phase I trial of 5-fluorouracil, leucovorin, and cisplatin in combination.
The ongoing evaluation of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in several tumors prompted a phase I clinical trial of cisplatin with 5-FU modulated by leucovorin. A total of 26 patients were treated with varying doses of 5-FU by continuous i.v. infusion for 5 days; 200 mg/m2 leucovorin was given by daily bolus injection for 5 days; and 20 mg/m2 cisplatin was infused over 2 h on each day of treatment. Courses were repeated every 21-28 days. The starting dose of 5-FU was 300 mg/m2. Poor-risk patients (extensive prior radiation, performance status of 2 or worse) did not tolerate the initial dose; the maximum tolerated dose of 5-FU in this group was 200 mg/m2 daily. Good-risk patients tolerated 300 mg/m2, but a majority had excessive toxicity at higher doses. The dose-limiting toxicity was gastrointestinal (mucositis/diarrhea) and/or myelosuppression; additional side effects included were nausea and vomiting (less than or equal to grade 2) and ataxia (one patient). Among 13 patients with colorectal cancer, 4 partial responses were observed. The marked reduction in the tolerable dose of 5-FU occasioned by the addition of modulating doses of leucovorin is noteworthy. The responses observed support further investigation of this regimen in phase II trials.
O'Dwyer
P J
PJ
Fox Chase Cancer Center, Department of Medical Oncology, Philadelphia, PA 19111.
Cornfeld
M J
MJ
Peter
R
R
Comis
R L
RL
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil