Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers

Inclusion Criteria

• •Histological evidence of prostate adenocarcinoma
• •Metastatic disease, either measurable (lymph nodes, hepatic lesion, pulmonary lesions with longest diameter \> or = 1 cm on spiral scan), or non measurable (bone metastasis)
• •Patients must:
• •* Have received hormonal therapy via surgical or chemical castration (LH-RH agonist) with or without anti-androgens. Anti-androgen withdrawal is recommended before inclusion, with an off-treatment period of at least 4 weeks. LH-RH agonist treatment must be continued.
• •* Have a relapse or disease refractory to hormonal treatment (defined by a testosterone level \< 0.5 µg/ml)
• •* Have neuroendocrine progression defined, whatever the PSA level, as:
• •* NSE and/or Chromogranin A \> 1.5 x upper limit of normal (ULN) with or without visceral metastases (liver, lung, lymph node)
• •* No increase of NSE or Chromogranin A, but visceral metastases (either hepatic, pleuro-pulmonary, or nodal) with cytological or histological confirmation of the presence of an undifferentiated or neuro-endocrine component of prostatic origin
• •Prior treatment by radiotherapy is allowed but radiation therapy must have been completed for at least 4 weeks before inclusion and irradiated areas must not represent more than 25% of marrow reserves
• •Prior treatment by estramustine is allowed but must have been stopped at least 4 weeks before inclusion
• •Age\> or = 18 years
• •Life expectancy\> or = 3 months
• •Karnofsky index\> or = 50%
• •Adequate haematological function: neutrophils\> or = 1.5 G/l, platelets\> or = 100 G/l, haemoglobin\> or = 8 g/dl. Use of erythropoietin is allowed.
• •Adequate liver function: bilirubin level within the institution's normal range, AST and ALT\< or = 1.5 ULN
• •Adequate renal function: creatinine clearance\> or = 40 ml/min (Gault and Cockroft method)
• •Signed written informed consent.