Androgen depletion and repletion as a means of potentiating the effect of cytotoxic chemotherapy in advanced prostate cancer

Andrea Manni, Richard J. Samten, Alice E. Boucher, Allan Lipton, Harold Harvey, Mary Simmonds, Robert Gordon, Thomas Rohner, Joseph Drago, John Wettlaufer, Leonard M. Glode

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Abstract

Seventy-five patients with stage D-2 prostate cancer refractory to orchiectomy have been entered in a controlled trial to test whether androgen priming enhances the efficacy of chemotherapy. All patients are treated with aminoglutethimide and hydrocortisone as a means of achieving medical adrenalectomy and are given cyclic i.v. chemotherapy with cytoxan, adriamycin and 5-fluorouracil. Patients in the stimulation arm (N = 39) receive, in addition, fluoxymesterone (5 mg p.o. b.i.d.) for 3 days before and on the day of chemotherapy. A similar response rate was observed in the stimulation and control arm (83% vs 74% respectively) when the analysis was restricted to evaluable patients. When all patients were included, a significantly higher response rate was observed in the control arm (64% vs 49%, P < 0.05) as a result of the larger fraction of unevaluable patients in the stimulation arm (41% vs 14%). Median duration of response is 9 months in the stimulation and 10 months in the control arm. Median overall survival in the stimulation and control group is 12 months and 16 months respectively. Significant toxicity consisting of exacerbation of bone pain and in two patients, development of reversible spinal cord compression was observed following androgen priming. Our results suggest that combined medical adrenalectomy and chemotherapy are highly effective in the treatment of advanced prostate cancer. Thus far, no additional benefit has been observed with androgen priming.

Original languageEnglish (US)
Pages (from-to)551-556
Number of pages6
JournalJournal of Steroid Biochemistry
Volume27
Issue number1-3
DOIs
StatePublished - 1987

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

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    Manni, A., Samten, R. J., Boucher, A. E., Lipton, A., Harvey, H., Simmonds, M., Gordon, R., Rohner, T., Drago, J., Wettlaufer, J., & Glode, L. M. (1987). Androgen depletion and repletion as a means of potentiating the effect of cytotoxic chemotherapy in advanced prostate cancer. Journal of Steroid Biochemistry, 27(1-3), 551-556. https://doi.org/10.1016/0022-4731(87)90353-0