Premium
Time to disease progression to evaluate a novel protein kinase C inhibitor, UCN‐01, in renal cell carcinoma
Author(s) -
Rini Brian I.,
Weinberg Vivian,
Shaw Vanessa,
Scott Janet,
Bok Robert,
Park John W.,
Small Eric J.
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20313
Subject(s) - medicine , renal cell carcinoma , clinical endpoint , progressive disease , clear cell renal cell carcinoma , circulating tumor cell , oncology , urology , cancer , chemotherapy , clinical trial , metastasis
Abstract BACKGROUND Renal cell carcinoma (RCC) is characterized by von Hippel‐Lindau gene inactivation and vascular endothelial growth factor (VEGF) overproduction. The mechanism of VEGF overproduction may involve protein kinase C (PKC) delta and zeta isoforms. UCN‐01 (7‐hydroxystaurosporine) is a selective inhibitor of PKC. Given the historically low objective response rate in RCC, time to disease progression (TTP) as an alternative endpoint was employed to evaluate the antitumor activity of UCN‐01 in RCC. METHODS Patients with progressive, metastatic RCC received UCN‐01 intravenously on Day 1 of each 21‐day cycle. The initial dose was 90 mg/m 2 and all subsequent doses were 45 mg/m 2 unless modified for toxicity. TTP was the primary endpoint, defined as the period from the first day of treatment until disease progression. Detection of circulating EpCAM‐positive renal carcinoma cells was undertaken for predictive or prognostic potential. RESULTS Twenty‐one patients were enrolled in this Phase II study. Accrual was halted after failure to reach a predetermined efficacy requirement with 7 patients remaining disease progression free after 4 months (6 cycles). The median TTP for all patients was 2.67 months (range, 0.4–7.6 months). There were no objective responses. Therapy was generally well tolerated. Thirteen patients had < 0.6 EpCAM‐positive cells/mL (considered negative) at all time points measured. Two patients had detectable EpCAM‐positive cells at a single time point with other measurements being negative. CONCLUSIONS TTP is a novel endpoint for the evaluation of agents in RCC. UCN‐01 did not demonstrate significant antitumor activity. No evidence for significant circulating EpCAM‐positive cells was found in this study cohort. Cancer 2004. © 2004 American Cancer Society.