Docetaxel and cisplatin in patients with metastatic androgen independent prostate cancer and circulating neuroendocrine markers.
OBJECTIVE
A link between neuroendocrine cell differentiation and resistance to androgen deprivation has been observed in prostate cancer, suggesting the possible efficacy of specific treatments. We assessed the efficacy and toxicity of a chemotherapy regimen combining docetaxel and cisplatin in men with androgen independent prostatic adenocarcinoma and circulating neuroendocrine markers.


METHODS
A total of 41 patients were treated with a combination of 75 mg/m(2) docetaxel and 75 mg/m(2) cisplatin every 3 weeks for a maximum of 6 cycles. The primary study end point was the neuroendocrine response rate, defined as a decrease in neuron specific enolase and/or chromogranin A to 50% or greater of the supranormal baseline serum value. Median followup was 40 months.


RESULTS
A median of 6 cycles per patient was delivered. A neuroendocrine response was observed in 13 patients (33%). The median response duration was 4 months (range 2 to 10). The prostate specific antigen response rate was 48%. A clinical benefit was observed in 45% of patients who required analgesics at study entry. The objective response rate was 41% in 29 patients with measurable metastases. Five patients had to stop therapy due to toxicity. The main side effects were cumulative asthenia and sensitive neuropathy. Median survival was 12 months (range 1 to 38).


CONCLUSIONS
Regarding the disappointing efficacy and significant toxicity observed in this study, the combination of docetaxel and cisplatin cannot be recommended in daily practice. Further studies are necessary to determine whether patients with circulating neuroendocrine markers require specific therapeutic approaches.
Culine
Stéphane
S
Centre Régional de Lutte Contre le Cancer Val d'Aurelle, Montpellier, France. stculine@valdorel.fnclcc.fr
El Demery
Mounira
M
Lamy
Pierre-Jean
PJ
Iborra
François
F
Avancès
Christophe
C
Pinguet
Frédéric
F
D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001285:Atropine; D014408:Biomarkers, Tumor / Q000097:blood*; D053379:Chromogranin A / Q000097:blood*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D006801:Humans; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D043823:Taxoids; D000077143:Docetaxel; D001285:Atropine; D010751:Phosphopyruvate Hydratase; D002945:Cisplatin