title: Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study.
abstract: OBJECTIVE
  The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles.
  
  
  OBJECTIVE
  To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial.
  
  
  METHODS
  The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors.
  
  
  METHODS
  Total number of docetaxel cycles delivered as an independent factor for OS.
  
  
  RESULTS
  Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P < .001), irrespective of lenalidomide treatment (HR, 1.060; 95% CI, 0.924-1.215; P = .41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P < .001).
  
  
  CONCLUSIONS
  These findings suggest that continuation of docetaxel chemotherapy contributes to the survival benefit. Prospective validation is warranted.
authors: Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam, the Netherlands.
authors: Ellen S
authors: ES
authors: de Morrée
authors: US Oncology Research, Houston, Texas3Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada.
authors: Nicholas J
authors: NJ
authors: Vogelzang
authors: Yale Cancer Center, Division of Oncology, Department of Medicine, New Haven, Connecticut.
authors: Daniel P
authors: DP
authors: Petrylak
authors: NSHI Dorozhnaya Clinical Hospital of OAO Russian Railways, Rostov-on-Don, Russia.
authors: Nikolay
authors: N
authors: Budnik
authors: Department of Uro-Oncology, Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland.
authors: Pawel J
authors: PJ
authors: Wiechno
authors: San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy.
authors: Cora N
authors: CN
authors: Sternberg
authors: Texas Oncology, Austin.
authors: Kevin
authors: K
authors: Doner
authors: University Hospital del Mar-IMIM, Barcelona, Spain10Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Joaquim
authors: J
authors: Bellmunt
authors: US Oncology Research, Houston, Texas11Rocky Mountain Cancer Centers, Aurora, Colorado.
authors: John M
authors: JM
authors: Burke
authors: Catalan Institute of Oncology, Department of Medical Oncology, Barcelona, Spain.
authors: Maria
authors: M
authors: Ochoa de Olza
authors: Department of Clinical Oncology, The Christie NHS Foundation Trust and Institute of Cancer Sciences, University of Manchester, Manchester, England.
authors: Ananya
authors: A
authors: Choudhury
authors: Department of Urology, Rechts der Isar Medical Center, Technische Universität München, München, Germany.
authors: Juergen E
authors: JE
authors: Gschwend
authors: State Institution of Healthcare " Regional Clinical Oncology Dispensary", Omsk, Russia.
authors: Evgeny
authors: E
authors: Kopyltsov
authors: Centre Léon Bérard, Department of Medical Oncology, Lyon, France.
authors: Aude
authors: A
authors: Flechon
authors: Department of Clinical Oncology, Royal Marsden Hospital, London, England.
authors: Nicolas
authors: N
authors: van As
authors: Medical Oncology Department, Groupe Hospitalier Universitaire Caremeau Place du Professeur Robert Debré, Nîmes, France.
authors: Nadine
authors: N
authors: Houede
authors: Celgene Corporation, Summit, New Jersey.
authors: Debora
authors: D
authors: Barton
authors: Celgene Corporation, Summit, New Jersey.
authors: Abderrahim
authors: A
authors: Fandi
authors: Celgene Corporation, Summit, New Jersey.
authors: Ulf
authors: U
authors: Jungnelius
authors: Celgene Corporation, Summit, New Jersey.
authors: Shaoyi
authors: S
authors: Li
authors: Celgene Corporation, Summit, New Jersey.
authors: Jack Shiansong
authors: JS
authors: Li
authors: Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam, the Netherlands.
authors: Ronald
authors: R
authors: de Wit
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D013792:Thalidomide; D000077269:Lenalidomide; D011241:Prednisone