title: Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  To evaluate the benefit of docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line docetaxel.
  
  
  METHODS
  We retrospectively reviewed the records of consecutive patients with mCRPC with a good response to first-line docetaxel [serum prostate specific antigen (PSA) decrease ≥50%; no clinical/radiological progression]. We analysed the impact of management at relapse (docetaxel rechallenge or non-taxane-based therapy) on PSA response, symptomatic response (performance status/pain/analgesic consumption), and overall survival (OS). We used multivariate stepwise logistic regression to analyse potential predictors of a favourable outcome.
  
  
  RESULTS
  We identified 270 good responders to first-line docetaxel. The median progression-free interval (PFI) was 6 months from the last docetaxel dose. At relapse, 223 patients were rechallenged with docetaxel (82.5%) and 47 received non-taxane-based therapy. There was no significant difference in median OS {18.2 [95% confidence interval (CI) 16.1-22.00] and 16.8 [95%CI 13.4-21.5] months, respectively, P = 0.35}. However, good PSA response and symptom relief/stable disease were more frequent on docetaxel rechallenge (40.4% vs 10.6%, P < 0.001 for PSA). A PFI of >6 months and added estramustine predicted a good PSA response and symptomatic response on docetaxel rechallenge but only a PFI of >6 months predicted longer OS. Haemoglobin (<13 g/dL) and pain were associated with reduced OS. Docetaxel rechallenge increased the incidence of grade ≥3 sensory neuropathy, nail disorders and asthenia/fatigue.
  
  
  CONCLUSIONS
  Docetaxel rechallenge is a management option for responders to docetaxel with a PFI of >6 months, but did not prolong survival. Potential benefits should be weighed against the risk of cumulative toxicity.
authors.affiliation: Department of Oncology, European Hospital Georges Pompidou and Paris Descartes University, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.forename: Gero
authors.initials: G
authors.lastname: Kramer
authors.forename: Orazio
authors.initials: O
authors.lastname: Caffo
authors.forename: Lorraine
authors.initials: L
authors.lastname: Creppy
authors.forename: Yohan
authors.initials: Y
authors.lastname: Loriot
authors.forename: Steinbjoern
authors.initials: S
authors.lastname: Hansen
authors.forename: Mats
authors.initials: M
authors.lastname: Holmberg
authors.forename: Frederic
authors.initials: F
authors.lastname: Rolland
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
authors.forename: Michael
authors.initials: M
authors.lastname: Krainer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D012074:Remission Induction; D019233:Retreatment; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel
keywords: castration-resistant; chemotherapy; docetaxel; prostate cancer