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

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, 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.

Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer.

Lancet Oncol. 2015 Jul;16(7):787-94. doi: 10.1016/S1470-2045(15)00011-X. Epub 2015 May 28.

Fizazi K1, Faivre L2, Lesaunier F3, Delva R4, Gravis G5, Rolland F6, Priou F7, Ferrero JM8, Houede N9, Mourey L10, Theodore C11, Krakowski I12, Berdah JF13,Baciuchka M14, Laguerre B15, Fléchon A16, Ravaud A17, Cojean-Zelek I18, Oudard S19, Labourey JL20, Chinet-Charrot P21, Legouffe E22, Lagrange JL23,Linassier C24, Deplanque G25, Beuzeboc P26, Davin JL27, Martin AL28, Habibian M28, Laplanche A2, Culine S29.

1Institut Gustave Roussy, Villejuif, France. 
2Institut Gustave Roussy, Villejuif, France.
3Centre François Baclesse, Caen, France.
4Institut de Cancérologie de l'Ouest, Angers, France.
5Institut Paoli Calmettes, Marseille, France.
6Institut de Cancérologie de l'Ouest, Nantes, France.
7Centre Hospitalier Départemental, La Roche-sur-Yon, France.
8Centre Antoine Lacassagne, Nice, France.
9Centre Hospitalier de Nimes, Nimes, France.
10Institut Claudius Regaud, Toulouse, France.
11Hôpital Foch, Paris, France.
12Centre Alexis Vautrin, Nancy, France.
13Clinique Sainte-Marguerite, Hyères, France.
14Centre Hospitalier La Timone, Marseille, France.
15Centre Eugène Marquis, Rennes, France.
16Centre Léon Bérard, Lyon, France.
17Hôpital Saint-André, Bordeaux, France.
18Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France.
19Hôpital Européen Georges Pompidou, Paris, France.
20CHU Dupuytren, Limoges, France.
21Centre Henri Becquerel, Rouen, France.
22Centre Médical Oncogard, Nimes, France.
23Hôpital Henri-Mondor, Créteil, France.
24Hôpital Bretonneau, Tours, France.
25Hôpital Saint-Joseph, Paris, France.
26Institut Curie, Paris, France.
27Clinique Sainte-Catherine, Avignon, France.
28Unicancer, Paris, France.
29Hôpital Saint-Louis, Paris, France.

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