Pilot study of angiotensin II receptor blocker in advanced hormone-refractory prostate cancer

Int J Clin Oncol. 2005 Dec;10(6):405-10. doi: 10.1007/s10147-005-0520-y.

Abstract

Background: We previously demonstrated that an angiotensin II receptor blocker (ARB) had the potential to inhibit cell proliferation of prostate cancer. In this study, we examined whether an ARB could elicit an antiproliferative effect on hormone-refractory prostate cancer, clinically.

Methods: Twenty-three patients with advanced hormone-refractory prostate cancer who had already received secondary hormonal therapy using dexamethasone, and who were no longer receiving conventional therapy, were enrolled. All of the patients received candesartan 8 mg once daily per os and, simultaneously, androgen ablation. Change in prostate-specific antigen (PSA) was determined as the primary endpoint. The secondary end-point was change in performance status (PS). To investigate angiotensin II type 1 (AT1) receptor expression in prostate cancer tissue, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed, using specimens, from untreated patients with prostate cancer.

Results: Eight patients (34.8%) showed responsive PSA changes; six showed a decrease immediately after starting administration and two showed a stable level of PSA. Six men with a PSA decline of more than 50% showed an improvement in PS. The mean time to PSA progression (TTPP) in responders was 8.3 months (range, 1-24 months). Half of the patients showed stable or improved PS during treatment. With regard to toxic effects, only one patient showed hypotension during treatment. The RT-PCR showed that AT1 receptor expression in well-differentiated adenocarcinoma was higher than that in poorly differentiated adenocarcinoma.

Conclusion: These data showed that an ARB had potential biological effects on prostate cancer, suggesting the usefulness of the cytostatic activity of such agents on recurrent prostate cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Tetrazoles / administration & dosage
  • Tetrazoles / therapeutic use

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antineoplastic Agents, Hormonal
  • Benzimidazoles
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Tetrazoles
  • Prostate-Specific Antigen
  • candesartan