title: Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone.
abstract: Abiraterone and cabazitaxel improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted an open-label phase I/II trial of cabazitaxel plus abiraterone to assess the antitumor activity and tolerability in patients with progressive mCRPC after docetaxel (phase I), and after docetaxel and abiraterone (phase II) (NCT01511536).
  
  
  
  The primary objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus abiraterone (phase I), and the prostate-specific antigen (PSA) response defined as a ≥ 50% decrease confirmed ≥3 weeks later with this combination (phase II).
  
  
  
  Ten patients were enrolled in the phase I component; nine were evaluable. No DLTs were identified. The MTD was established as the approved doses for both drugs (cabazitaxel 25 mg/m2 every 3 weeks and abiraterone 1000 mg once daily). Daily abiraterone treatment did not impact on cabazitaxel clearance. Twenty-seven patients received cabazitaxel plus abiraterone plus prednisone (5 mg twice daily) in phase II. The median number of cycles administered (cabazitaxel) was seven (range: 1-28). Grade 3-4 treatment-emergent adverse events included asthenia (in 5 patients; 14%), neutropenia (in 5 patients; 14%) and diarrhea (in 3 patients; 8%). Nine patients (24%) required dose reductions of cabazitaxel. Of 26 evaluable patients, 12 achieved a PSA response [46%; 95% confidence interval (CI): 26.6-66.6%]. Median PSA-progression-free survival was 6.9 months (95% CI: 4.1-10.3 months). Of 14 patients with measurable disease at baseline, 3 (21%) achieved a partial response per response evaluation criteria in solid tumors.
  
  
  
  The combination of cabazitaxel and abiraterone has a manageable safety profile and shows antitumor activity in patients previously treated with docetaxel and abiraterone.
authors.affiliation: Department of Drug Development, Gustave Roussy Cancer Campus, University of Paris Sud, Villejuif, France.|Department of Medical Oncology, Gustave Roussy Cancer Campus, University of Paris Sud, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mateo
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, University of Paris Sud, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Pezaro
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, University of Paris Sud, Villejuif, France.
authors.forename: L
authors.initials: L
authors.lastname: Albiges
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Mehra
authors.affiliation: Department of Drug Development, Gustave Roussy Cancer Campus, University of Paris Sud, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Varga
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Comprehensive Cancer Center Yale School of Medicine, New Haven.
authors.forename: D P
authors.initials: DP
authors.lastname: Petrylak
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Attard
authors.affiliation: Sanofi Genzyme, Cambridge, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, University of Paris Sud, Villejuif, France.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: de Bono
mesh_terms: D000368:Aged; D000736:Androstenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D043823:Taxoids; D000077143:Docetaxel; C552428:cabazitaxel; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: abiraterone; cabazitaxel; combination; prostate cancer