Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC).
In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m2, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration.
The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%).
The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit.
EudraCT 2014-000175-43 - NCT02453009.
European journal of cancer (Oxford, England : 1990). 2021 Aug 03 [Epub ahead of print]
Orazio Caffo, Cinzia Ortega, Franco Nolè, Donatello Gasparro, Claudia Mucciarini, Michele Aieta, Vittorina Zagonel, Roberto Iacovelli, Ugo De Giorgi, Gaetano Facchini, Antonello Veccia, Erica Palesandro, Elena Verri, Sebastiano Buti, Giorgia Razzini, Giovanni Bozza, Marco Maruzzo, Chiara Ciccarese, Giuseppe Schepisi, Sabrina Rossetti, Francesca Maines, Lucia Fratino, Paola Ermacora, Maurizio Nicodemo, Monica Giordano, Donata Sartori, Daniela Scapoli, Roberto Sabbatini, Giovanni Lo Re, Franco Morelli, Alessandro D'Angelo, Isabella Vittimberga, Paolo Lippe, Francesco Carrozza, Caterina Messina, Luca Galli, Francesca Valcamonico, Camillo Porta, Giovanni Pappagallo, Massimo Aglietta
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