title: Combining carboplatin and etoposide in docetaxel-pretreated patients with castration-resistant prostate cancer: a prospective study evaluating also neuroendocrine features.
abstract: 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.
  
  
  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/m(2)/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 > or =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.
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Loriot
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.forename: M
authors.initials: M
authors.lastname: Gross-Goupil
authors.forename: M
authors.initials: M
authors.lastname: Di Palma
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.forename: A
authors.initials: A
authors.lastname: Bossi
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D000077143:Docetaxel; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011379:Prognosis; D011446:Prospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D005047:Etoposide; D016190:Carboplatin