Incidence and Characteristics of Antiandrogen Withdrawal Syndrome in Prostate Cancer after Treatment with Chlormadinone Acetate

Abstract

Objectives: In patients with progressive prostate cancer who have been treated with surgical or medical castration plus an antiandrogen, antiandrogen withdrawal can result in a significant decline in serum prostate-specific antigen (PSA). Although the incidence of antiandrogen withdrawal syndrome after combination treatment with the nonsteroidal antiandrogen flutamide has been thoroughly documented, the phenomenon clearly occurs in many other combination therapies and is presently being widely investigated. This paper would like to contribute to this effort by describing the endocrine withdrawal phenomenon in patients treated with combinations of castration plus chlormadinone acetate, ethynylestradiol or estramustine phosphate. Materials and Methods: Clinical records of 68 prostate cancer patients who had been treated with surgical castration plus the administration of chlormadinone acetate, ethynylestradiol or estramustine phosphate, and who had shown clinical progression associated with a steady increase in serum PSA, were investigated. Forty-one cases were evaluable for changes in PSA after discontinuation of the hormonal agents. Results: Of 28 patients who had been treated with chlormadinone acetate, 12 (42.9%) revealed 50% or more decline in PSA level following withdrawal of the agent. Among these, 5 cases (17.9%) showed subjective and/or objective improvements. There was no significant difference in histological grade of the tumor at diagnosis, mode of progression, time interval from the start of endocrine therapy to discontinuation of the hormonal agents, or PSA levels at withdrawal of the agents between patients who did develop antiandrogen withdrawal syndrome and those who did not. Conclusion: When a steady increase in serum PSA is noted in a prostate cancer patient who has been treated with castration plus a steroidal antiandrogen, discontinuation of the antiandrogen may benefit the patient.