Phase Ib/II Trial of Gemcitabine, Cisplatin, and Lenalidomide as First-Line Therapy in Patients With Metastatic Urothelial Carcinoma

Background. Outcomes with current chemotherapy in metastatic urothelial carcinoma (MUC) remain poor. Lenalidomide, an antiangiogenic and immunomodulatory agent, enhances the effects of chemotherapy in preclinical studies. In this phase Ib/II study, we sought to determine a tolerable dose of lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC and to explore the safety and activity of this regimen. Methods. Patients with chemotherapy-naive MUC received gemcitabine 1,000mg/m(2) on days 1 and 8 and cisplatin 70 mg/m(2) on day 1 every 21 days. In phase Ib, there were four planned escalating dose levels of lenalidomide (10, 15, 20, and 25 mg) daily on days 1-14. Results. Seven patients received GCL in phase Ib. The dose of lenalidomide was not escalated beyond 10 mg because of cytopenias requiring repeated dose delays and reductions. Two additional patients were enrolled in phase II, but the study was ultimately terminated due to poor tolerability and slow accrual. The most frequent grade >= 3 adverse events were cytopenias and diarrhea. Three of the nine patients experienced an objective response (one complete response, two partial responses). Conclusion. Chronic administration of the GCL regimen was poorly tolerated because of additive and cumulative myelo-suppression.