Population-based Analysis of Treatment Toxicity Among Men With Castration-resistant Prostate Cancer: A Phase IV Study

Urology. 2018 Mar:113:138-145. doi: 10.1016/j.urology.2017.08.067. Epub 2017 Nov 27.

Abstract

Objective: To assess the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments at a population level, among all patients in Ontario particularly treated with newer agents, including abiraterone, enzalutamide, docetaxel, and cabazitaxel.

Methods: We performed a population-based, retrospective cohort study of 2439 men aged ≥65 years treated for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003 to 2015 in Ontario, Canada. Our primary outcome was treatment-related toxicity, defined as hospitalizations and emergency room (ER) visits during mCRPC treatment. Based on toxicity profiles identified during phase III trials, we further identified specific treatment-related toxicity. We calculated hazard ratios (HRs) using multivariable Cox proportional hazards models with time-varying exposures.

Results: Abiraterone and enzalutamide exposure were not associated with any-cause (P = .19 and .52, respectively) or treatment-related (P = .45 and .64, respectively) toxicities. In contrast, docetaxel exposure was associated with an increased risk of any-cause (HR 1.29, 95% confidence interval [CI] 1.15-1.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicities. Cabazitaxel exposure was associated with a significant risk of treatment-related toxicity (HR 5.94, 95% CI 1.87-18.92) but not any-cause toxicity (HR 2.37, 95% CI 0.59-9.63).

Conclusion: Among patients with mCRPC, we failed to show any increased risk of hospitalizations and ER visits for treatment-related complications for abiraterone or enzalutamide. In contrast, treatment with intravenous chemotherapeutic agents was associated with an increased risk of hospitalizations and ER visits to manage these complications.

Publication types

  • Clinical Trial, Phase IV

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes / administration & dosage
  • Androstenes / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Benzamides
  • Canada
  • Cohort Studies
  • Docetaxel / administration & dosage
  • Docetaxel / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Emergency Service, Hospital / statistics & numerical data*
  • Hospitalization / statistics & numerical data*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Maximum Tolerated Dose
  • Multivariate Analysis
  • Nitriles
  • Ontario
  • Phenylthiohydantoin / administration & dosage
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives
  • Population Surveillance
  • Prognosis
  • Proportional Hazards Models
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Treatment Outcome

Substances

  • Androstenes
  • Benzamides
  • Nitriles
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • cabazitaxel
  • enzalutamide
  • abiraterone