title: Phase 1b Study of Abiraterone Acetate Plus Prednisone and Docetaxel in Patients with Metastatic Castration-resistant Prostate Cancer.
abstract: Coadministration of docetaxel and abiraterone acetate plus prednisone (AA + P) may benefit patients with metastatic castration-resistant prostate cancer (mCRPC) because of complementary mechanisms of action. COU-AA-206 was a phase 1b study to determine the safe dose combination of docetaxel and AA + P in three cohorts of chemotherapy-naïve mCRPC patients. Twenty-two patients received escalating doses of docetaxel plus AA + P. The primary endpoint was the proportion of patients with a dose-limiting toxicity (DLT) between weeks 2 and 7. The recommended phase 2 dose (RP2D) was the highest safe combination of docetaxel plus AA + P. Prostate-specific antigen (PSA) changes and intensive pharmacokinetic parameters for each drug were evaluated. Docetaxel 75mg/m2+ AA 1000mg + P 10mg was deemed the RP2D, with DLT in one of six patients. PSA declines from baseline of ≥50% and ≥90% were observed for 85.7% and 66.7% of patients, respectively. During median follow-up of 14.5 mo, eight patients had PSA progression and six had radiographic progression or died. Systemic exposure was comparable for docetaxel and abiraterone when given alone or in combination. Studies are ongoing to confirm the efficacy of potent androgen receptor-targeted therapy plus taxane in early mCRPC.
  
  
  
  The combination of hormonal therapy and chemotherapy may improve outcomes in men with metastatic prostate cancer. This study demonstrates the ability to combine the hormonal therapy agent abiraterone acetate, plus prednisone, and the chemotherapy drug docetaxel with an acceptable side effect profile. A high rate of prostate-specific antigen decline was seen, but the study was small and additional research is needed before this becomes a standard approach.
authors: Weill Cornell Medical College and Meyer Cancer Center, New York, NY, USA. Electronic address: stt2007@med.cornell.edu.
authors: Scott T
authors: ST
authors: Tagawa
authors: Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors: Edwin M
authors: EM
authors: Posadas
authors: University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors: Justine
authors: J
authors: Bruce
authors: Columbia University Medical Center, New York, NY, USA.
authors: Emerson A
authors: EA
authors: Lim
authors: Yale Cancer Center, New Haven, CT, USA.
authors: Daniel P
authors: DP
authors: Petrylak
authors: Janssen Research & Development, Los Angeles, CA, USA.
authors: Weimin
authors: W
authors: Peng
authors: Janssen Research & Development, San Diego, CA, USA.
authors: Thian
authors: T
authors: Kheoh
authors: Janssen Research & Development, Los Angeles, CA, USA.
authors: Scott
authors: S
authors: Maul
authors: Janssen Research & Development, Beerse, Belgium.
authors: Johan W
authors: JW
authors: Smit
authors: Janssen Research & Development, Raritan, NJ, USA.
authors: Martha D
authors: MD
authors: Gonzalez
authors: Janssen Research & Development, Beerse, Belgium.
authors: Peter
authors: P
authors: De Porre
authors: Janssen Research & Development, Los Angeles, CA, USA.
authors: NamPhuong
authors: N
authors: Tran
authors: Weill Cornell Medical College and Meyer Cancer Center, New York, NY, USA.
authors: David M
authors: DM
authors: Nanus
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; D011241:Prednisone
keywords: Abiraterone acetate; Androgen receptor; Combination; Docetaxel; Drug-drug interaction; Metastatic castration-resistant prostate cancer; Pharmacokinetics; Safety; Toxicity