Clinical effectiveness of docetaxel for castration-sensitive prostate cancer in a real-world population-based analysis

Prostate. 2019 Feb;79(3):281-287. doi: 10.1002/pros.23733. Epub 2018 Oct 28.

Abstract

Background: Adding docetaxel to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) has known efficacy, with an overall survival benefit in Phase III clinical trials. The effectiveness of docetaxel with ADT in the general patient population remains undefined.

Patients and methods: We conducted a population-based retrospective review using the British Columbia Provincial Pharmacy Database. To be included, patients had to have castration-sensitive prostate cancer not previously treated (except in the adjuvant setting) and have received at least one cycle of docetaxel, with complete records available for review. Safety and clinical effectiveness were evaluated.

Results: From April 2015 to February 2017, we identified 183 cases; 156 met inclusion criteria. Most patients had high-volume disease (80%). All 6 planned docetaxel cycles were delivered in 126 cases (81%). Dose reductions and delays were required in 39% and 16% of cases. Grade 3-4 adverse events were noted in 40%, with no treatment-related deaths. The rate of febrile neutropenia was 18% and was significantly associated with the presence of high-volume disease (P = 0.038). PSA ≤ 0.2 ng/L was achieved in 27% of patients after 6 months of ADT and maintained in 16% after 12 months. Patients with over 20 bone metastases had worse time to castration resistant prostate cancer (CRPC) and time to treatment for CRPC, and a trend toward worse overall survival. CRPC developed in 41% within 1 year, with a median time to CRPC of 14.4 months. Treatment for CRPC was given in 84 cases, with 90% receiving either abiraterone or enzalutamide in the first-line, with a PSA decline ≥50% occurring in 47%.

Conclusions: The effectiveness of docetaxel with ADT in a general population of patients with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the published studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to reported outcomes.

Keywords: clinical effectiveness; docetaxel; prostate cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Docetaxel / administration & dosage*
  • Docetaxel / adverse effects
  • Humans
  • Kallikreins
  • Male
  • Middle Aged
  • Prostate-Specific Antigen
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Docetaxel
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen