title: Multiple rechallenges for castration-resistant prostate cancer patients responding to first-line docetaxel: assessment of clinical outcomes and predictive factors.
abstract: OBJECTIVE
  To describe the feasibility and efficacy of multiple sequential rechallenges and analyze the predictive factors that may aid in selecting patients who are more likely to respond. Several studies have demonstrated the feasibility and activity of a single docetaxel rechallenge in patients with castration-resistant prostate cancer (CRPC), thus providing an additional opportunity for treatment in docetaxel-sensitive CRPC patients in clinical practice.
  
  
  METHODS
  CRPC patients who completed first-line docetaxel therapy without disease progression have been offered a docetaxel rechallenge, and the responders have undergone further rechallenges until the appearance of docetaxel resistance. We assessed their clinical outcomes and evaluated all the variables potentially capable of predicting the response to rechallenge by means of uni- and multivariate analysis.
  
  
  RESULTS
  Forty-six consecutive patients underwent 92 rechallenges. The overall biochemical response rate (prostate-specific antigen [PSA] reduction >50%) was 66%. Median overall survival was 32 months with a projected 2-year overall survival from the first docetaxel administration of 77.5%. Multivariate analysis showed that the time slope-log PSA, the time from the previous cycle, and the response to the previous cycle were predictive of the response to a rechallenge.
  
  
  CONCLUSIONS
  A docetaxel rechallenge may be safely repeated several times in CRPC patients and in selected patients could improve disease control. The predictive factors found in our analysis may help select the most appropriate strategy in the light of the availability of active second-line drugs.
authors.affiliation: Department of Medical Oncology, Santa Chiara Hospital, Trento, Italy. orazio.caffo@apss.tn.it
authors.forename: Orazio
authors.initials: O
authors.lastname: Caffo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pappagallo
authors.forename: Sonia
authors.initials: S
authors.lastname: Brugnara
authors.forename: Alessia
authors.initials: A
authors.lastname: Caldara
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: di Pasquale
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferro
authors.forename: Michela
authors.initials: M
authors.lastname: Frisinghelli
authors.forename: Viviana
authors.initials: V
authors.lastname: Murgia
authors.forename: Lucianna Maria
authors.initials: LM
authors.lastname: Russo
authors.forename: Barbara
authors.initials: B
authors.lastname: Soini
authors.forename: Francesco
authors.initials: F
authors.lastname: Valduga
authors.forename: Antonello
authors.initials: A
authors.lastname: Veccia
authors.forename: Enzo
authors.initials: E
authors.lastname: Galligioni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen