title: Exploring the Clinical Benefit of Docetaxel or Enzalutamide After Disease Progression During Abiraterone Acetate and Prednisone Treatment in Men With Metastatic Castration-Resistant Prostate Cancer.
abstract: BACKGROUND
  Abiraterone acetate (AA) has demonstrated improved outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). However, data are lacking on the effect of AA on subsequent efficacy of enzalutamide or docetaxel.
  
  
  METHODS
  We included men with mCRPC who received AA and subsequent enzalutamide or docetaxel by August 12, 2013. Patients were separated into 3 groups: group A, treated with AA then enzalutamide before chemotherapy; group B, treated with AA then docetaxel; and group C, treated with AA and enzalutamide after chemotherapy. The primary objective was to describe the response and overall survival with subsequent therapy.
  
  
  RESULTS
  There were 28 evaluable patients who received enzalutamide after AA (9 in group A and 19 in group C) and 13 patients who received docetaxel after AA (group B). Group A patients had more visceral disease and higher baseline prostate-specific antigen (PSA) levels, and group C men had a higher level of pain and multiple poor prognostic features. Median progression-free survival was 3.6, 5.1, and 2.8 months, respectively, and median overall survival was 8.5, not reached, and 9.6 months, respectively. A ≥ 50% PSA decline was achieved in 11%, 63%, and 5% of group A, B, and C patients, respectively. Radiographic or clinical progression as best response was noted in 55.5%, 30.8%, and 68.4% in each respective group.
  
  
  CONCLUSIONS
  In this chart review of consecutive men with progressive mCRPC after AA, we found modest activity for enzalutamide and docetaxel, with clear cross-resistance for AA and enzalutamide. These data might inform the complex treatment decisions after AA treatment.
authors.affiliation: Duke Cancer Institute, Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke University Medical Center, Durham, NC.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: University of California - San Francisco, San Francisco, CA.
authors.forename: Mallika S
authors.initials: MS
authors.lastname: Dhawan
authors.affiliation: Duke Cancer Institute, Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke University Medical Center, Durham, NC.
authors.forename: Patrick
authors.initials: P
authors.lastname: Healy
authors.affiliation: Duke Cancer Institute, Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke University Medical Center, Durham, NC.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.affiliation: Duke Cancer Institute, Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke University Medical Center, Durham, NC.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Harrison
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC.
authors.forename: Jorge
authors.initials: J
authors.lastname: Oldan
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC.
authors.forename: Bennett
authors.initials: B
authors.lastname: Chin
authors.affiliation: Duke Cancer Institute, Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke University Medical Center, Durham, NC. Electronic address: andrew.armstrong@duke.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
mesh_terms: D000069501:Abiraterone Acetate; D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011241:Prednisone / Q000494:pharmacology* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D011859:Radiography; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; C089740:abiraterone; D011241:Prednisone
keywords: Abiraterone; Castration resistant prostate cancer; Cross-resistance; Docetaxel; Enzalutamide