1. 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
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Nadine Houede, Claude Linassier, Philippe Beuzeboc, Paule Chinet-Charrot, Laura Faivre, Loic Mourey, Aude Flechon, Frank Priou, Gael Deplanque, Jean-Marc Ferrero, Jean-Louis Davin, Christine Theodore, Muriel Habibian, Brigitte Laguerre, Remy Delva, Anne-Laure Martin, Ivan Krakowski, Agnès Laplanche, Karim Fizazi, Frederic Rolland, Jean-Luc Labourey, Stéphane Culine, Jean-François Berdah, Gwenaelle Gravis, François Lesaunier, Isabelle Cojean-Zelek, Eric Legouffe, Alain Ravaud, Marjorie Baciuchka, Stéphane Oudard, Jean-Léon Lagrange, Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Hôpital Foch [Suresnes], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Hôpital privé Toulon Hyères : Sainte Marguerite, Hôpital de la Timone [CHU - APHM] (TIMONE), CRLCC Eugène Marquis (CRLCC), Centre Léon Bérard [Lyon], Hôpital Saint-André, Groupe Hospitalier Diaconesses Croix Saint-Simon, Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Limoges, CRLCC Henri Becquerel, ONCOGARD - NIMES, Institut de Cancérologie du GARD (Instit Cancéro - GARD), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Saint-Joseph, Institut Curie, Institut Sainte Catherine [Avignon], UNICANCER [Paris], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Curie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université Côte d'Azur (UCA)-UNICANCER, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)
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Male ,medicine.medical_specialty ,Maximum Tolerated Dose ,Population ,030232 urology & nephrology ,Urology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Docetaxel ,Kaplan-Meier Estimate ,Disease-Free Survival ,Drug Administration Schedule ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Invasiveness ,education ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,education.field_of_study ,Dose-Response Relationship, Drug ,business.industry ,Standard treatment ,Goserelin ,Prostatic Neoplasms ,Cancer ,Androgen Antagonists ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Survival Analysis ,3. Good health ,Surgery ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Estramustine ,Taxoids ,France ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies ,medicine.drug - Abstract
International audience; 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.
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- 2015
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