Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors.

Abstract

Triapine administered at a dose of 96 mg/m(2) by 2-h i.v. infusion daily for 5 days on an every-other-week schedule demonstrates an acceptable safety profile. Serum concentrations that surpass in vitro tumor growth-inhibitory concentrations are achieved for brief periods of time each day and are sufficient to produce myelosuppression, the expected consequence of ribonucleotide reductase inhibition. Phase II trials are indicated but will proceed with a daily-for-4-days schedule to reduce the incidence of grade 4 leukopenia. The safety profile also supports the initiation of Phase I combination trials with other anticancer agents.