Effects of intermittent androgen suppression on androgen-dependent tumors. Apoptosis and serum prostate-specific antigen

Cancer. 1993 May 1;71(9):2782-90. doi: 10.1002/1097-0142(19930501)71:9<2782::aid-cncr2820710916>3.0.co;2-z.


Background: Since postcastration progression of tumors to an androgen-independent state appears to be linked to the cessation of androgen-induced differentiation of tumorigenic stem cells, the authors hypothesized that the replacement of androgens at the end of a period of apoptotic regression might result in the regeneration of differentiated tumor cells with further apoptotic potential.

Methods and results: To determine the effect of intermittent exposure of androgens on the androgen-dependent Shionogi carcinoma, the tumor was transplanted into a succession of male mice, each of which was castrated when the estimated tumor weight became about 3 g. After the tumor had regressed to 30% of the original weight, it was transplanted into the next noncastrated male. This cycle of transplantation and castration-induced apoptosis was repeated successfully four times before growth became androgen-independent during the fifth cycle. In four of Stage C and three of Stage D patients with prostate cancer, androgen withdrawal was initiated with cyproterone acetate (100 mg/d) and diethylstilbestrol (0.1 mg/d) and then maintained with cyproterone acetate in combination with the luteinizing hormone-releasing hormone agonist, goserelin acetate (3.6 mg/month). After 6 or more months of suppression of serum prostate-specific antigen (PSA) into the normal range, treatment was interrupted for 2 to 11 months. After recovery of testicular function, androgen-withdrawal therapy was resumed when serum PSA increased to a level of about 20 micrograms/l. This cycle was repeated sequentially to a total of two to four times over treatment periods of 21 to 47 months with no loss of androgen dependence.

Conclusions: These results demonstrate that intermittent androgen suppression can be used to induce multiple apoptotic regressions of a tumor; they also suggest that the cyclic effects of such treatment on prostate cancer can be followed by the sequential measurement of serum PSA levels.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Aged
  • Animals
  • Apoptosis / drug effects*
  • Cyproterone Acetate / therapeutic use
  • Diethylstilbestrol / therapeutic use
  • Gonadotropin-Releasing Hormone / administration & dosage
  • Goserelin / administration & dosage
  • Humans
  • Male
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / surgery
  • Mice
  • Middle Aged
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Neoplasms, Hormone-Dependent / blood
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplasms, Hormone-Dependent / surgery
  • Orchiectomy
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Testosterone / blood


  • Goserelin
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Cyproterone Acetate
  • Diethylstilbestrol
  • Prostate-Specific Antigen