Enzalutamide treatment in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy and abiraterone acetate

Scand J Urol. 2014 Jun;48(3):268-75. doi: 10.3109/21681805.2013.860189. Epub 2013 Nov 21.

Abstract

Objective: The aim of this study was to record prostate-specific antigen (PSA) response and overall survival (OS) for a group of metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide following progression after abiraterone treatment in the post-chemotherapy setting.

Material and methods: Twenty-four mCRPC patients with progression after abiraterone treatment following primary docetaxel therapy received enzalutamide 160 mg/day. The percentage PSA response was recorded following first line docetaxel, abiraterone and enzalutamide treatment. Fischer's exact test, Mann-Whitney U test and linear regression model were used to test for differences in PSA response.

Results: All patients had a follow-up of at least 3 months. The median PSA response following 1 month of enzalutamide was -12% (range -56% to 76%), while the median best PSA response was -22% (-76% to 76%). Forty-six percent had a greater than 30% decrease in PSA. The PSA response to enzalutamide did not correlate with the number of prior cancer treatments (p = 0.57), time from diagnosis to mCRPC (p = 0.11) or prior response to docetaxel (p = 0.67). However, patients treated with second line cabazitaxel had an inferior PSA response to enzalutamide (p = 0.03), and there was a trend for the PSA response to abiraterone to correlate with the PSA response to the succeeding enzalutamide (B = 0.22, p = 0.05). The median OS was 4.8 months.

Conclusions: Previous abiraterone therapy is associated with a less marked fall in PSA following enzalutamide therapy in post-chemotherapy mCRPC patients compared with reported results in randomized trials. Larger prospective studies of sequencing are warranted.

Keywords: abiraterone; castration-resistant prostate cancer; enzalutamide; post-chemotherapy; sequencing.

MeSH terms

  • Abiraterone Acetate
  • Aged
  • Androstadienes / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Cohort Studies
  • Compassionate Use Trials
  • Disease-Free Survival
  • Docetaxel
  • Humans
  • Kallikreins / metabolism*
  • Linear Models
  • Male
  • Middle Aged
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Taxoids / therapeutic use
  • Treatment Failure
  • Treatment Outcome

Substances

  • Androstadienes
  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • cabazitaxel
  • enzalutamide
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen
  • Abiraterone Acetate