A Prospective Audit of Intermittent Anti-Androgen verses Pituitary Blockade Suggests a Bipolar Androgen Type Strategy May Be Safe in Untreated Prostate Cancer

Urol Int. 2018;100(2):172-180. doi: 10.1159/000485255. Epub 2017 Dec 22.

Abstract

Objective: A locally advanced Gleason 4 + 4 prostate cancer patient who was on self-medication with intermittent anti-androgen monotherapy (iAAm) over 14 years suggested that raised testosterone was not dangerous and this suggestion needed investigating.

Patients: Others who were on AA continuously were recruited to ongoing audit of intermittent hormone therapy (IHT) and iAAm outcomes were compared with intermittent LHRH therapy (iLHRH or iMAB).

Results: Between 1994 and 2007, 111 patients sought IHT because of side effects of treatment. Forty-two M0 patients received IHT with iLHRHm or iMAB and 33 received iAAm (31 of these were M0). PSA nadir below 4 was necessary for entry. Overall survival was 87, 72 and 67% with iAAm and 73, 56 and 43% with iLHRH/MAB at 5, 8 and 10 years respectively. Overall survival was 61, 55 and 33% continued on iAAm and 56, 41, and 32% on iLHRH/MAB at 5, 8, and 10 years respectively. Multivariable analysis and matched case control analysis confirm that the maintenance of advantage for iAAm Testosterone levels in patients on iAAm compared to iLHRH therapy was more intense throughout treatment.

Conclusion: These results complement recent progress in using bipolar androgen therapy to reverse castration resistance and add to the increasing acceptance that controlled testosterone exposure might be relevant in hormone-naïve patients.

Keywords: Anti-androgen; Bipolar androgen therapy; Intermittent; Prostate cancer.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / adverse effects
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Administration Schedule
  • Gonadotropin-Releasing Hormone / agonists*
  • Gonadotropin-Releasing Hormone / metabolism
  • Humans
  • Kallikreins / blood
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Medical Audit
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Odds Ratio
  • Pituitary Gland / drug effects*
  • Pituitary Gland / metabolism
  • Proportional Hazards Models
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Time Factors
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen