• Karim Fizazi, Laura Faivre, François Lesaunier, Remy Delva, Gwenaëlle Gravis, Frédéric Rolland, Frank Priou, Jean-Marc Ferrero, Nadine Houede, Loïc Mourey, Christine Theodore, Ivan Krakowski, Jean-François Berdah, Marjorie Baciuchka, Brigitte Laguerre, Aude Fléchon, Alain Ravaud, Isabelle Cojean-Zelek, Stéphane Oudard, Jean-Luc Labourey, Paule Chinet-Charrot, Eric Legouffe, Jean-Léon Lagrange, Claude Linassier, Gaël Deplanque, Philippe Beuzeboc, Jean-Louis Davin, Anne-Laure Martin, Muriel Habibian, Agnès Laplanche, and Stéphane Culine.
• Institut Gustave Roussy, Villejuif, France. Electronic address: karim.fizazi@gustaveroussy.fr.
• Lancet Oncol. 2015 Jul 1; 16 (7): 787794787-94.

BackgroundEarly risk-stratified chemotherapy is a standard treatment for breast, colorectal, and lung cancers, but not for high-risk localised prostate cancer. Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer. We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer.MethodsWe did this randomised phase 3 trial at 26 hospitals in France. We enrolled patients with treatment-naive prostate cancer and at least one risk factor (ie, stage T3-T4 disease, Gleason score of ≥8, prostate-specific antigen concentration >20 ng/mL, or pathological node-positive). All patients underwent a staging pelvic lymph node dissection. Patients were randomly assigned (1:1) to either androgen deprivation therapy (ADT; goserelin 10·8 mg every 3 months for 3 years) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m(2) and estramustine 10 mg/kg per day on days 1-5, every 3 weeks, or ADT only. The randomisation was done centrally by computer, stratified by risk factor. Local treatment was administered at 3 months. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing. This study is registered with ClinicalTrials.gov, number NCT00055731.FindingsWe randomly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group. Median follow-up was 8·8 years (IQR 8·1-9·7). 88 (43%) of 207 patients in the ADT plus docetaxel and estramustine group had an event (relapse or death) versus 111 (54%) of 206 in the ADT only group. 8-year relapse-free survival was 62% (95% CI 55-69) in the ADT plus docetaxel and estramustine group versus 50% (44-57) in the ADT only group (adjusted hazard ratio [HR] 0·71, 95% CI 0·54-0·94, p=0·017). Of patients who were treated with radiotherapy and had data available, 31 (21%) of 151 in the ADT plus docetaxel and estramustine group versus 26 (18%) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect (p=0·61). We recorded no excess second cancers (26 [13%] of 207 vs 22 [11%] of 206; p=0·57), and there were no treatment-related deaths.InterpretationDocetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer. Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival.FundingLigue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer.Copyright © 2015 Elsevier Ltd. All rights reserved.

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