A phase II study of depsipeptide in refractory metastatic renal cell cancer

Background: Therapeutic options for renal cell cancer are inadequate. Depsipeptide is a histone deacetylase inhibitor with promising preclinical and early clinical activity. Patients and Methods: Patients with refractory renal cell cancer with normal organ function and no history of significant cardiovascular disease were enrolled on a mufti-institutional, single-arm, phase II study. Patients received depsipeptide 13 mg/m(2) 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 initial 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. Results: The 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%). Conclusion: Depsipeptide at this dose and schedule does not have sufficient activity for further investigation in this patient population.