Intermittent vs continuous docetaxel therapy in patients with metastatic castration-resistant prostate cancer - a phase III study (PRINCE)

BJU Int. 2018 Nov;122(5):774-782. doi: 10.1111/bju.14239. Epub 2018 May 6.

Abstract

Objective: To investigate non-inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

Patient and methods: The investigator initiated randomised phase III study included 187 chemotherapy-naïve patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2 ) or 3-weekly (75 mg/m2 ). The primary endpoint was 1-year survival, which was tested for non-inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression-free survival (PFS), median time to treatment failure (TTF), and toxicity.

Results: Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non-inferiority criteria for 1-year survival (two-sided 95% confidence interval, -0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13-486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited.

Conclusion: Intermittent docetaxel chemotherapy was non-inferior to continuous therapy for 1-year survival; non-inferiority in regard to OS was not reached.

Keywords: castration-resistant prostate cancer; docetaxel; intermittent therapy; multicentre study; non-inferiority; phase III trial.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Docetaxel* / administration & dosage
  • Docetaxel* / adverse effects
  • Docetaxel* / therapeutic use
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology

Substances

  • Antineoplastic Agents
  • Docetaxel