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 (≤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 response observed support further investigation of this regimen in phase II trials.

DOI: 10.1007/BF00689097

3 Figures and Tables


Citations per Year

273 Citations

Semantic Scholar estimates that this publication has 273 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Odwyer1990PhaseIT, title={Phase I trial of 5-fluorouracil, leucovorin, and cisplatin in combination}, author={Peter J O'dwyer and Mark J. Cornfeld and Ruth Peter and Robert L. Comis}, journal={Cancer Chemotherapy and Pharmacology}, year={1990}, volume={27}, pages={131-134} }