Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers

• Status: Completed
• Trial end date: 2010-01-01
• Target enrollment: 0
• Participant gender: Male

Summary

The aim of our study is to assess the efficacy and toxicity of a chemotherapy regimen combining carboplatin and etoposide in patients with metastatic hormone-resistant prostate cancer and neuro-endocrine differentiation. Eligible patients are treated with the combination of carboplatin AUC4 on day 1 and etoposide 100 mg/m2 on day 1, day 2 and day 3 repeated every 3 weeks for a maximum of 6 cycles. Efficacy endpoints include Prostate Specific Antigen (PSA) and neuro-endocrine marker response (defined as a 50% or greater decrease from baseline serum values), objective response rate (according to RECIST criteria), and toxicity.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Leon Berard
• Treatments: Carboplatin; Etoposide; Etoposide phosphate; Hormones

Criteria

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.

Exclusion Criteria:

• Patients having no> 1.5 x ULN increase of at least one neuro-endocrine marker (NSE or chromogranin A) and no cytological or histological (undifferentiated or neuro-endocrine type) evidence of visceral metastasis (hepatic, pleuro-pulmonary, or nodal)

• History of other malignancies, other than curatively treated basal cell skin carcinoma or any other curatively treated cancer with no sign of recurrence within 5 years

• Symptomatically uncontrolled brain metastasis

• Interstitial radiation therapy (using strontium or samarium) within the previous 3 months

• Prior treatment with platinum salts or etoposide. Other chemotherapy regimens are allowed provided that the last dose has been administered> or = 4 weeks prior to inclusion.

• Concomitant treatment with other anti-cancer drugs, except corticoid or LH-RH agonist injections

• Peripheral neuropathy> or = 2 (NCI-CTCAE)

• Uncontrolled progressive thrombo-embolic disease

• Uncontrolled infection

• Medical history of acute myocardial infection or uncontrolled angina pectoris, or hypertension or uncontrolled arrythmia

• Inclusion in another clinical trial

• Impaired follow-up for social, geographical, familial or psychological reasons

• Any other unstable disease.