This study is a phase II trial of carboplatin plus etoposide in prostate cancer (CaP) patients with progressive, anaplastic metastatic castration-resistant prostate cancer (mCRPC). The patients included had evidence of neuroendocrine cells with expression of neuropeptides and lack of androgen receptor expression.
Between 2005 and 2008, 60 patients were enrolled. All had castrate levels of testosterone on androgen deprivation therapy (ADT) and no more than two prior chemotherapy regimens. All had metastasis. Etoposide and carboplatin were given until disease progression, severe toxicity or patient refusal or non-compliance. Response rate and toxicities were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated. A median of 4 treatment cycles was delivered. Most discontinuations were due to disease progression (85.5%). In the first step, 5 of 19 patients had an objective response. In the final analysis, 55 patients were assessable and 5 (9.1%) of the 55 treated patients and 4 of 46 (8.7%) patients with measurable disease had objective responses. Thirty-six of the 55 men (65.4%) had progressive disease and 17 (31%) had non-progressive disease at the end of treatment. By serum markers, 4.8-31% of cases had a neuroendocrine response. Eight patients had a PSA response >50% and 42% had stable values or <50% regression. PFS was 2.9 months and OS was 9.6 months. Forty-eight of 55 patients died of progressive disease and one from febrile neutropenia. LDH level >2 was significant in multivariate analysis for OS. PSA >100ng/ml was the only poor prognostic factor significantly associated with PFS in multivariate analysis. Toxicity was grade 3-4 in up to 65% of patients.
They concluded that the low response rate and high toxicity make this regimen unfavorable.
Fléchon A, Pouessel D, Ferlay C, Perol D, Beuzeboc P, Gravis G, Joly F, Oudard S, Deplanque G, Zanetta S, Fargeot P, Priou F, Droz JP, Culine S
Ann Oncol. 2011 Mar 24. Epub ahead of print.