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
2 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
3 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
4 IPC - Institut Paoli-Calmettes
5 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
6 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
7 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
8 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
9 Oncopole Claudius Regaud
10 Hôpital Foch [Suresnes]
11 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
12 Hôpital privé Toulon Hyères : Sainte Marguerite
13 TIMONE - Hôpital de la Timone [CHU - APHM]
14 CRLCC - CRLCC Eugène Marquis
15 Centre Léon Bérard [Lyon]
16 Hôpital Saint-André [Bordeaux]
17 Groupe Hospitalier Diaconesses Croix Saint-Simon
18 HEGP - Hôpital Européen Georges Pompidou [APHP]
19 CHU Limoges
20 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
21 ONCOGARD - NIMES
22 Hôpital Henri Mondor
23 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
24 Centre hospitalier Saint-Joseph [Paris]
25 Institut Curie [Paris]
26 Institut Sainte Catherine [Avignon]
27 UNICANCER [Paris]
28 Hôpital Saint-Louis
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Résumé
BACKGROUND: 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. METHODS: 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(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. FINDINGS: 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 vs 22 [11%] of 206; p=0·57), and there were no treatment-related deaths. INTERPRETATION: 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. FUNDING: Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer.