Annals of Oncology Advance Access originally published online on January 29, 2009
Annals of Oncology 2009 20(4):703-708; doi:10.1093/annonc/mdn694
urogenital tumors |
Combining carboplatin and etoposide in docetaxel-pretreated patients with castration-resistant prostate cancer: a prospective study evaluating also neuroendocrine features
Department of Medicine, Institut Gustave Roussy, Villejuif, France
* Correspondence to: Dr K. Fizazi, Department of Medicine, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94800 Villejuif Cedex, France. Tel: +33-1-42-11-62 64; Fax: +33-1-42-11-52 38; E-mail: fizazi{at}igr.fr
Background: There is currently no standard treatment for patients with castration-resistant prostate cancer (CRPC) whose disease progresses after docetaxel-based chemotherapy. The purpose of this study was to prospectively assess the anticancer activity and tolerance of the carboplatin–etoposide combination in this setting while evaluating neuroendocrine (NE) features.
Patients and methods: Patients with CRPC and metastases who experienced failure after first-line docetaxel-based chemotherapy were treated with carboplatin (area under the curve 5, day 1) and etoposide (80 mg/m2/day from days 1 to 3), repeated every 3 weeks. The association between serum chromogranin A (CgA), neuron-specific enolase (NSE), prostate-specific antigen-doubling time (PSADT), and treatment efficacy was studied.
Results: Forty patients with CRPC who had received docetaxel with (n = 20) or without (n = 20) estramustine received the carboplatin–etoposide combination as second-line chemotherapy. A prostate-specific antigen (PSA) response defined as a PSA decline 
50% was achieved in nine patients (23%). Median progression-free survival (PFS) was 2.1 months (range 0.6–9.6) and median overall survival was 19 months (range 2.1–27.7). Pain response was achieved in 15 (53%) of 28 assessable patients. Toxicity, including mainly grades 3–4 anaemia (25%) and febrile neutropenia in only 2% of patients, was manageable. Baseline CgA, NSE, or PSADT were not significant predictors for response or PFS. The PSA response rates were 18% and 31% in patients with normal and elevated serum CgA, respectively. It was 25% and 20%, respectively, in patients with normal and elevated serum NSE.
Conclusions: Combining carboplatin and etoposide as second-line chemotherapy in patients with CRPC is active and well tolerated in spite of a limited PFS. Activity was observed in CRPC with and without NE features.
Key words: chemotherapy, chromogranin A, neuron-specific enolase, prostate cancer
Received for publication May 27, 2008. Revision received October 1, 2008. Accepted for publication October 2, 2008.
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