Enzalutamide With Radiation Therapy for Intermediate-Risk Prostate Cancer: A Phase 2 Study

Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1416-1422. doi: 10.1016/j.ijrobp.2021.02.027. Epub 2021 Feb 23.

Abstract

Purpose: Androgen deprivation therapy (ADT) is often used as adjuvant treatment with radiation therapy (RT) for intermediate-risk prostate cancer. ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, antiandrogen monotherapy has been generally better tolerated. This study aimed to assess the effectiveness of enzalutamide (an antiandrogen) monotherapy with RT for the treatment of intermediate-risk prostate cancer.

Methods and materials: This trial was an open-label, phase 2 study of 6 months of enzalutamide monotherapy with external beam RT for intermediate-risk prostate cancer. Enzalutamide was initiated 2 months before external beam RT. The primary endpoint was prostate-specific antigen (PSA) response measured at the end of enzalutamide administration at the 6-month timepoint. Secondary endpoints included assessment of toxicity and changes in anthropomorphic body measurement, sexual function, and metabolism. The sample size was 64 patients. The hypothesis was that if ≥60% of the patients did not achieve a PSA nadir of ≤0.2 ng/mL, the study results would be deemed negative.

Results: The results met the prespecified endpoint for efficacy in that PSA values ≤0.2 ng/mL were observed in 49 of 64 patients (77%), and 60 of 64 patients (94%) had PSA values ≤0.5ng/mL. The most frequent adverse events were hypertension and gynecomastia. There were no changes in anthropomorphic body measurements and only modest erectile dysfunction.

Conclusions: Using PSA response as an endpoint, enzalutamide monotherapy may be as effective as ADT in combination with external beam RT for patients with intermediate-risk prostate cancer, and it is associated with fewer side effects. Randomized trials comparing enzalutamide with ADT are justified.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / therapeutic use*
  • Androgens / blood
  • Benzamides / adverse effects
  • Benzamides / therapeutic use*
  • Body Composition / drug effects
  • Body Fat Distribution
  • Gynecomastia / chemically induced
  • Humans
  • Hypertension / chemically induced
  • Male
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / therapeutic use*
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Risk
  • Testosterone / blood
  • Time Factors

Substances

  • Androgen Antagonists
  • Androgens
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • Testosterone
  • enzalutamide
  • Prostate-Specific Antigen