A safety, tolerability, and pharmacokinetic (PK) study of GW572016 in patients with solid tumors

Abstract

3179 Background: GW572106 is a reversible inhibitor of ErbB1/ErbB2 tyrosine kinases. This phase I monotherapy study evaluated safety, tolerability, and PK in patients with advanced solid tumors at once (QD) and twice daily (BID) dosing schedules. Methods: Patients (pts) were administered GW572106 on a QD or BID continuous schedule. QD doses ranged from 175 to 1800 mg and BID doses were 500, 750, and 900 mg per dose. In addition to standard evaluations, serial MUGAs were obtained. PK on days 1 and 14 and disease assessments every 8 weeks (RECIST criteria) were obtained. Results: 81 pts with various carcinomas were enrolled; 64 pts (39 QD, 25 BID) included in safety and disease assessment; 57 included in PK. Median age was 62 yrs; 39 males/25 females. The majority of drug-related AEs were grade I (75% of pts QD, 71% pts BID). Diarrhea was the most frequent AE (17% QD, 29% BID of pts). Two pts had grade 3 diarrhea at 900 mg BID. Other AEs were fatigue (16%), nausea (16%) and rash (9%) on QD and nausea (11%) ...