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 - 30/06/15
, Laura Faivre a, François Lesaunier, MD b, Remy Delva, MD c, Gwenaëlle Gravis, MD d, Frédéric Rolland, MD e, Frank Priou, MD f, Jean-Marc Ferrero, ProfMD g, Nadine Houede, MD h, Loïc Mourey, MD i, Christine Theodore, MD j, Ivan Krakowski, MD k, Jean-François Berdah, MD l, Marjorie Baciuchka, MD m, Brigitte Laguerre, MD n, Aude Fléchon, MD o, Alain Ravaud, ProfMD p, Isabelle Cojean-Zelek, MD q, Stéphane Oudard, ProfMD r, Jean-Luc Labourey, MD s, Paule Chinet-Charrot, MD t, Eric Legouffe, MD u, Jean-Léon Lagrange, ProfMD v, Claude Linassier, ProfMD w, Gaël Deplanque, MD x, Philippe Beuzeboc, MD y, Jean-Louis Davin, MD z, Anne-Laure Martin, PharmD aa, Muriel Habibian aa, Agnès Laplanche, MD a, Stéphane Culine, ProfMD abSummary |
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/m2 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.
Le texte complet de cet article est disponible en PDF.Plan
Vol 16 - N° 7
P. 787-794 - juillet 2015 Retour au numéro
Article précédent
- Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA trials
- Aimée R Kreimer, Frank Struyf, Maria Rowena Del Rosario-Raymundo, Allan Hildesheim, S Rachel Skinner, Sholom Wacholder, Suzanne M Garland, Rolando Herrero, Marie-Pierre David, Cosette M Wheeler, Costa Rica Vaccine Trial and the PATRICIA study groups †
- Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial
- Encouse B Golden, Arpit Chhabra, Abraham Chachoua, Sylvia Adams, Martin Donach, Maria Fenton-Kerimian, Kent Friedman, Fabio Ponzo, James S Babb, Judith Goldberg, Sandra Demaria, Silvia C Formenti
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?