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.


METHODS
Patients 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 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 >or= 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 clear-cell 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%).


CONCLUSIONS
Depsipeptide at this dose and schedule does not have sufficient activity for further investigation in this patient population.
Stadler
Walter M
WM
Department of Medicine, University of Chicago, IL 60637-1470, USA. wstadler@medicine.bsd.uchicago.edu
Margolin
Kim
K
Ferber
Sandy
S
McCulloch
William
W
Thompson
John A
JA
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D047630:Depsipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure
D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; C087123:romidepsin