Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Fizazi, Karim; Faivre, Laura; Lesaunier, François; Delva, Remy; Gravis, Gwenaëlle; Rolland, Frédéric; Priou, Frank; Ferrero, Jean-Marc; Houede, Nadine; Mourey, Loïc; Theodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Fléchon, Aude; Ravaud, Alain; Cojean-Zelek, Isabelle; Oudard, Stéphane; Labourey, Jean-Luc; Chinet-Charrot, Paule; Legouffe, Eric; Lagrange, Jean-Léon; Linassier, Claude; Deplanque, Gaël; Beuzeboc, Philippe; Davin, Jean-Louis; Martin, Anne-Laure; Habibian, Muriel; Laplanche, Agnès; Culine, Stéphane;
• Is Part Of: Lancet oncology. Volume 16:Issue 7(2015:Jul.)
• Page Start: 787
• Page End: 794
• Publication Date: 2015-07
• Subjects: Oncology -- Periodicals; Neoplasms -- Periodicals; Cancérologie -- Périodiques; Oncologie; Oncology; Periodicals; Electronic journals; 616.994005
• DOI: 10.1016/S1470-2045(15)00011-X
• Languages: English
• ISSNs: 1470-2045

Abstract

<abstract abstract-type="author" id="ceab10"> <title id="cestitle10">Summary</title> <sec> <title id="cestitle20">Background</title> <p id="spara150">Early 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.</p> </sec> <sec> <title id="cestitle30">Methods</title> <p id="spara160">We 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<sup>2</sup> 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 <ext-link ext-link-type="unknown" id="interrefs10" xlink:type="simple" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, number <ext-link ext-link-type="unknown" id="interrefs20" xlink:type="simple" xlink:href="ctgov:NCT00055731" xmlns:xlink="http://www.w3.org/1999/xlink">NCT00055731</ext-link>.</p> </sec> <sec> <title id="cestitle40">Findings</title> <p id="spara170">We 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 <italic>vs</italic> 22 [11%] of 206; p=0·57), and there were no treatment-related deaths.</p> </sec> <sec> <title id="cestitle50">Interpretation</title> <p id="spara180">Docetaxel-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.</p> </sec> <sec> <title id="cestitle60">Funding</title> <p id="spara190">Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer.</p> </sec> </abstract>