Pether Michael, Goldenberg S Larry, Bhagirath Kapil, Gleave Martin
The Prostate Centre at Vancouver General Hospital, Division of Urology, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
Can J Urol. 2003 Apr;10(2):1809-14.
This report will review the long-term follow-up of a prospective Phase II evaluation of intermittent androgen suppression in the treatment of prostate cancer. Specifically, this analysis will address completed cycle characteristics, the concept of prolonged off-treatment cycles, the time to cancer progression, cancer-specific survival and the association between PSA and bone scan changes.
A total of 102 patients have been entered into this protocol. Treatment was initiated with combined androgen blockade and continued for 6 months or longer to reach a serum PSA nadir. Medication was then withheld until the serum PSA increased to predetermined trigger points based on initial parameters. Each cycle of treatment and no-treatment was repeated until the regulation of PSA became biochemically androgen independent.
One hundred two patients have been commenced on IAS with an average follow-up time of 219 weeks (range: 14.5 to 588). Ninety-one patients have completed at least one therapeutic cycle with a total of 188 completed cycles available for analysis. The average time off therapy (percentage time off therapy) for cycles 1, 2, 3 and 4 was 13 months (53%), 11 months (51%), 10 months (47%) and 8 months (45%), respectively. A prolonged off-treatment time of greater than 72 weeks was observed in 33 (18%) of all completed cycles, and was most common in the men being treated for radiation failure stage C. Progression and survival data was calculated for the entire trial cohort (n=102). The average time to androgen independent progression in the 29 (28%) patients who progressed was 194 weeks. Death from prostate cancer occurred in 19 (18%) patients at an average of 258 weeks following treatment initiation. A review of bone scans revealed 22 events of newly detected lesions, all but 2 of which were preceded by a rise in serum PSA.
Longer duration follow-up of a single cohort continues to support IAS as a viable treatment option for men with prostate cancer. This approach affords an improved quality of life when the patient is off therapy, with reduced toxicity and costs. There is a trend toward extended times to progression and death compared to contemporary studies of continuous androgen suppression. Randomized, prospective protocols are currently underway to determine whether survival is affected in a beneficial or adverse way in men with locally recurrent or metastatic cancer.
本报告将回顾一项关于间歇性雄激素抑制治疗前列腺癌的前瞻性II期评估的长期随访情况。具体而言，本分析将探讨已完成周期的特征、延长停药周期的概念、癌症进展时间、癌症特异性生存率以及PSA与骨扫描变化之间的关联。
共有102例患者进入本方案。治疗始于联合雄激素阻断，并持续6个月或更长时间以达到血清PSA最低点。然后停药，直到血清PSA根据初始参数升高到预定触发点。每个治疗和非治疗周期重复进行，直到PSA的调节在生化上变为雄激素非依赖性。
102例患者开始接受间歇性雄激素抑制治疗，平均随访时间为219周（范围：14.5至588周）。91例患者完成了至少一个治疗周期，共有188个完整周期可供分析。第1、2、3和4周期的平均停药时间（停药时间百分比）分别为13个月（53%）、11个月（51%）、10个月（47%）和8个月（45%）。在所有完成的周期中，33个（18%）观察到延长的停药时间超过72周，这在接受C期放疗失败治疗的男性中最为常见。计算了整个试验队列（n = 102）的进展和生存数据。29例（28%）进展患者中雄激素非依赖性进展的平均时间为194周。19例（18%）患者死于前列腺癌，平均在开始治疗后258周。对骨扫描的回顾显示有22例新检测到的病变事件，其中除2例之外，所有事件之前血清PSA均升高。
对单个队列更长时间的随访继续支持间歇性雄激素抑制作为前列腺癌男性可行的治疗选择。这种方法在患者停药时可提高生活质量，同时降低毒性和成本。与当代持续雄激素抑制研究相比，有进展和死亡时间延长的趋势。目前正在进行随机前瞻性方案，以确定局部复发或转移性癌症男性的生存是否受到有益或不利影响。
