A Phase II Study of Depsipeptide in Refractory Metastatic Renal Cell Cancer

BackgroundTherapeutic options for renal cell cancer are inadequate. Depsipeptide is a histone deacetylase inhibitor with promising preclinical and early clinical activity.Patients and MethodsPatients with refractory renal cell cancer with normal organ function and no history of significant cardiovascular disease were enrolled on a multi-institutional, single-arm, phase II study. Patients received depsipeptide 13 mg/m2 intravenously over 4 hours on days 1, 8, and 15 of a 28-day cycle with disease reevaluation performed every 8 weeks. One response in the Initials 16 enrolled patients was required for full accrual to 25 patients, from which 5 responses needed to be observed in order to consider the agent appropriate for further study. Toxicity was assessed using National Cancer Institute Common Toxicity Criteria, version 2.0.ResultsThe 29 evaluable patients, who were accrued so that 25 patients who received ≥ 3 doses of depsipeptide could be observed, were heavily pretreated with a median of 2 previous systemic therapies and a 2-year median duration of metastatic disease. Twenty-four had clearcell histology. The most common serious toxicities were fatigue, nausea, vomiting, and anemia. Two patients developed a prolonged QTc interval, one patient each developed grade 3 atrial fibrillation and tachycardia, and there was 1 sudden death. Two patients experienced an objective response (1 complete response) for an overall response rate of 7% (95% CI, 0.8%- 23%).ConclusionDepsipeptide at this dose and schedule does not have sufficient activity for further investigation in this patient population.