Phase II clinical and pharmacokinetic (PK) trial of zalypsis (Z) in patients with urothelial carcinoma (UC) progressing after a first-line platinum-based regimen.

e15001 Background: Platinum-based chemotherapy (CT) is beneficial as first-line treatment of advanced UC. However, the majority of patients develop recurrent disease with poor long-term survival rates. Attempts to improve second-line treatments have evaluated single agents and multi-drug combinations, neither of which has managed to improve survival or achieve durable responses. Z is a cytotoxic agent that induces apoptosis by acting at cell cycle level, has DNA-binding properties and inhibits transcriptional responses. Z has shown anti-tumor activity in vitro and in vivo in xenograft models. Based on the activity observed in a phase I study (1PR and 2 SD) in advanced bladder cancer, we have designed a phase II study to explore the efficacy of Z in this setting. Methods: Patients with histologically-confirmed advanced or metastatic UC, who had failed one prior line of platinum-based CT, with proven progression or relapse before study entry, were included. Patients were treated with a Z intravenous infusio...