ANDROGEN RECEPTOR GENE AMPLIFICATION IN A RECURRENT PROSTATE-CANCER AFTER MONOTHERAPY WITH THE NONSTEROIDAL POTENT ANTIANDROGEN CASODEX (BICALUTAMIDE) WITH A SUBSEQUENT FAVORABLE RESPONSE TO MAXIMAL ANDROGEN BLOCKADE

Objective: We recently found amplification of the androgen receptor (A R) gene in similar to 30% of locally recurrent prostate carcinomas fro m patients treated by conventional androgen deprivation (castration) t herapy, whereas none of the untreated primary prostate tumors showed t his amplification, This suggests that AR gene amplification was select ed during androgen deprivation therapy, The present case study represe nts our initial approach to evaluate the role that AR amplification ma y play in therapy resistance after other forms of endocrine therapy, M aterial and Methods: Specimens from both a primary and a subsequent lo cally recurrent tumor were studied for amplification of the AR gene by fluorescence in situ hybridization from a prostate cancer patient who experienced tumor progression after monotherapy with the potent antia ndrogen bicalutamide (Casodex, a trade mark, the property of Zeneca Lt d), Results and Conclusions: High-level amplification of the AR gene w as found in the recurrent tumor, whereas no evidence of amplification was found in the primary tumor, After recurrence, the patient first re ceived chemotherapy (ifosfamide) for 15 weeks with no response, follow ed by maximal androgen blockade (MAB), The latter therapy resulted in a favorable short-term response, This case study has the following imp lications which warrant further research: (1) AR amplification may be selected not only by. castration but also by therapy with a competitiv e peripheral androgen-receptor-blocking agent, and (2) recurrent tumor s with AR amplification may be particularly likely to benefit from MAB as a second-line therapy.