Goldenberg S L, Bruchovsky N, Gleave M E, Sullivan L D, Akakura K
Department of Surgery, University of British Columbia, Vancouver, Canada.
Urology. 1995 May;45(5):839-44; discussion 844-5. doi: 10.1016/s0090-4295(99)80092-2.
To test the feasibility of using intermittent androgen suppression in the treatment of prostate cancer by taking advantage of the reversible action of medical castration.
Observations were made on a group of 47 patients (clinical Stage D2, 14; D1, 10; C, 19; B2, 2; and A2, 2) with a mean follow-up time of 125 weeks. Treatment was initiated with combined androgen blockade and continued for at least 6 months until a serum prostate-specific antigen (PSA) nadir was observed. Medication was then withheld until the serum PSA increased to a mean value between 10 and 20 ng/mL. This cycle of treatment and no treatment was repeated until the regulation of serum PSA became androgen independent.
The first two treatment cycles lasted 73 and 75 weeks, with a mean time off therapy of 30 and 33 weeks and an overall mean percentage time off therapy of 41% and 45%, respectively. The mean time to achieve a nadir level of serum PSA was 20 weeks in cycle 1 and 18 weeks in cycle 2. Serum testosterone returned to the normal range within 8 weeks (range, 1 to 26) of stopping treatment. The off-treatment period in both cycles was associated with an improvement in sense of well-being and the recovery of libido and potency in the men who reported normal or near-normal sexual function before the start of therapy. In 7 patients with Stage D2 disease, the cancer progressed to an androgen-independent state. The mean and median times to progression were 128 weeks and 108 weeks, respectively. Seven patients have died, 1 from a noncancer-related illness, with mean and median overall survival times of 210 weeks and 166 weeks, respectively.
Prostate cancer is amenable to control by intermittent androgen suppression. This approach affords an improved quality of life when the patient is off therapy. It also results in reduced toxicity and cost of treatment and possibly delays tumor progression. Whether survival is affected in a beneficial or adverse way remains to be studied in a randomized, prospective study.
利用药物去势的可逆作用，测试间歇性雄激素抑制疗法治疗前列腺癌的可行性。
对47例患者（临床分期D2期14例、D1期10例、C期19例、B2期2例、A2期2例）进行观察，平均随访时间为125周。治疗始于联合雄激素阻断，持续至少6个月，直至观察到血清前列腺特异性抗原（PSA）最低点。然后停药，直到血清PSA升高至10至20 ng/mL的平均值。重复这种治疗与不治疗的周期，直到血清PSA的调节变为雄激素非依赖性。
前两个治疗周期分别持续73周和75周，平均停药时间分别为30周和33周，总体平均停药时间百分比分别为41%和45%。达到血清PSA最低点水平的平均时间在第1周期为20周，在第2周期为18周。停药后8周内（范围1至26周）血清睾酮恢复至正常范围。两个周期的停药期均与幸福感改善以及报告在治疗开始前性功能正常或接近正常的男性的性欲和性能力恢复相关。7例D2期疾病患者的癌症进展为雄激素非依赖性状态。进展的平均时间和中位时间分别为128周和108周。7例患者死亡，1例死于非癌症相关疾病，总体平均生存时间和中位生存时间分别为210周和166周。
前列腺癌可通过间歇性雄激素抑制得到控制。这种方法在患者停药时可提高生活质量。它还能降低治疗毒性和成本，并可能延迟肿瘤进展。间歇性雄激素抑制疗法对生存率是产生有益还是有害影响，仍有待在随机前瞻性研究中进行探究。
