A phase II study of depsipeptide (Dep) in patients (pts) with metastatic renal cell cancer (RCC)

Abstract

4669 Background: Metastatic RCC is poorly responsive to current available systemic therapies. Multiple genes thought to be important in RCC development and progression are inactivated by methylation and histone deacetylation. Dep is a natural product with potent histone deacetylase inhibitory and anti-tumor properties in preclinical and phase I studies. Methods: Pts with metastatic RCC and normal organ function who failed prior cytokine therapy were treated with 13 mg/m2 Dep weekly (wk) for 3 wks out of 4. The statistical plan specified an initial enrollment of 16 pts with further enrollment to 25 if at least 1 RECIST response was observed. Results: 30 pts were enrolled from 3 institutions of which 29 received at least 1 dose and are evaluable. Baseline characteristics included M/F (21/8), median (range) age 59 (41–79), time from diagnoses 2.4 yrs (0.6–15.2), and number of prior therapies 2 (2–12). Major grade 3/4 toxicities included fatigue (5), nausea/vomiting (4), anemia (3), anorexia (2), dehydration (2), cardiac rhythm disturbances without sequelae (2), and asymptomatic prolonged QTc (1). Grade 1/2 constitutional symptoms were common with nausea (27), fatigue (21), dysgeusia (8), dizziness (6), rigors (5), and myalgias (5) reported. Ten pts required dose delay/adjustment and 12 pts discontinued therapy early (including 3 prior to response evaluation) at least in part due to toxicities. There was one CR and one unconfirmed PR (7% overall response rate), but on review, the pt with CR had a baseline lesion of only 9mm. Neither responder had any unique pathologic characteristics. Median time to progression was 12 weeks. Conclusions: The response and toxicity profile indicate that further investigation of Dep in RCC should focus on identifying predictors of response, possible growth inhibitory (rather than cytotoxic) properties, or activity in rationally derived combinations. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gloucester Gloucester