Phase I clinical trial of combined therapy with 5-FU (NSC 19893) and cis-platinum (II) diaminedichloride (NSC 119875)

Abstract

Thirty-one loading courses of 5-FU and cis-platinum (II) diaminedichloride (CPD) were given to 27 patients with a variety of malignancies. Up to 16 mg/kg/day of 5-FU and 2.5 mg/kg of the platinum were reached with minimal toxicity. Nausea (27/31) and vomiting (23/31) were the most frequent symptoms, with few experiencing diarrhea (5) or stomatitis (1). Urinary abnormalities were transient, generally returning to baseline levels by completion of therapy. Leukopenia appeared less commonly during the loading courses than during weekly 5-FU and monthly CPD maintenance. Platelet counts consistently remained between 100,000 and 200,000 during maintenance. Asymptomatic high-tone hearing losses were detected by repeat audiograms in 2 patients. Although the primary objective of the program was to determine combined toxicity, four brief and five continuing responses were noted.