Karim Fizazi1, Laura Faivre2, François Lesaunier3, Remy Delva4, Gwenaëlle Gravis5, Frédéric Rolland6, Frank Priou7, Jean-Marc Ferrero8, Nadine Houede9, Loïc Mourey10, Christine Theodore11, Ivan Krakowski12, Jean-François Berdah13, Marjorie Baciuchka14, Brigitte Laguerre15, Aude Fléchon16, Alain Ravaud17, Isabelle Cojean-Zelek18, Stéphane Oudard19, Jean-Luc Labourey20, Paule Chinet-Charrot21, Eric Legouffe22, Jean-Léon Lagrange23, Claude Linassier24, Gaël Deplanque25, Philippe Beuzeboc26, Jean-Louis Davin27, Anne-Laure Martin28, Muriel Habibian28, Agnès Laplanche2, Stéphane Culine29. 1. Institut Gustave Roussy, Villejuif, France. Electronic address: karim.fizazi@gustaveroussy.fr. 2. Institut Gustave Roussy, Villejuif, France. 3. Centre François Baclesse, Caen, France. 4. Institut de Cancérologie de l'Ouest, Angers, France. 5. Institut Paoli Calmettes, Marseille, France. 6. Institut de Cancérologie de l'Ouest, Nantes, France. 7. Centre Hospitalier Départemental, La Roche-sur-Yon, France. 8. Centre Antoine Lacassagne, Nice, France. 9. Centre Hospitalier de Nimes, Nimes, France. 10. Institut Claudius Regaud, Toulouse, France. 11. Hôpital Foch, Paris, France. 12. Centre Alexis Vautrin, Nancy, France. 13. Clinique Sainte-Marguerite, Hyères, France. 14. Centre Hospitalier La Timone, Marseille, France. 15. Centre Eugène Marquis, Rennes, France. 16. Centre Léon Bérard, Lyon, France. 17. Hôpital Saint-André, Bordeaux, France. 18. Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France. 19. Hôpital Européen Georges Pompidou, Paris, France. 20. CHU Dupuytren, Limoges, France. 21. Centre Henri Becquerel, Rouen, France. 22. Centre Médical Oncogard, Nimes, France. 23. Hôpital Henri-Mondor, Créteil, France. 24. Hôpital Bretonneau, Tours, France. 25. Hôpital Saint-Joseph, Paris, France. 26. Institut Curie, Paris, France. 27. Clinique Sainte-Catherine, Avignon, France. 28. Unicancer, Paris, France. 29. Hôpital Saint-Louis, Paris, France.
Abstract
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.
RCT Entities:
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.
Authors: Quentin Adams; Karolyn M Hopfensperger; Yusung Kim; Xiaodong Wu; Weiyu Xu; Hemant Shukla; James McGee; Joseph M Caster; Ryan T Flynn Journal: Int J Radiat Oncol Biol Phys Date: 2018-08-06 Impact factor: 7.038
Authors: Matthew J O'Shaughnessy; Sean M McBride; Hebert Alberto Vargas; Karim A Touijer; Michael J Morris; Daniel C Danila; Vincent P Laudone; Bernard H Bochner; Joel Sheinfeld; Erica S Dayan; Lawrence P Bellomo; Daniel D Sjoberg; Glenn Heller; Michael J Zelefsky; James A Eastham; Peter T Scardino; Howard I Scher Journal: Urology Date: 2016-11-22 Impact factor: 2.649