Bruchovsky N, Goldenberg S L, Akakura K, Rennie P S
Department of Cancer Endocrinology, British Columbia Cancer Agency, Vancouver Clinic, Canada.
Cancer. 1993 Sep 1;72(5):1685-91. doi: 10.1002/1097-0142(19930901)72:5<1685::aid-cncr2820720532>3.0.co;2-3.
In response to the first administration of a luteinizing hormone-releasing hormone (LHRH) agonist, the secretion of pituitary gonadotropin increases sharply and gives rise to a transient surge in the concentration of serum testosterone. This effect reaches a peak 4 to 7 days after the start of therapy and results in the onset of clinical symptoms and signs of tumor flare in 5% to 10% of patients.
To determine whether the effects of the LHRH-induced flare reaction are preventable, cyproterone acetate (100 mg) and low-dose diethylstilbestrol (0.1 mg) were administered daily for 4 weeks to inhibit the pituitary before the initiation of therapy with a depot LHRH agonist, goserelin acetate (3.6 mg every 4 weeks). Diethylstilbestrol was stopped after 8 weeks to eliminate associated minor toxicity while administration of cyproterone acetate was continued to suppress vasomotor symptoms. Twenty-four men with histologically confirmed prostate cancer were enrolled in the study: 6 with Stage C, 2 with Stage D1, and 16 with Stage D2 disease.
Lead-in therapy reduced the concentration of serum testosterone into the castrate range within 1 week, and no significant change was observed in the mean level after administration of goserelin acetate. Neither was there an effect on the initial rate of normalization of serum prostate specific antigen (PSA); normal PSA values were obtained in 50% of patients after 10 weeks and in 70% after 32 weeks. In the subgroup of patients with Stage D2 disease, longer median survival was predicted by a normal serum PSA, either stable or decreasing, after 32 weeks of treatment. The regimen was well tolerated with a low incidence of hot flushes.
These results imply that in the absence of LHRH-induced tumor flare, prognosis is related to the ability of therapy to maintain a PSA nadir in the normal range.
在首次给予促黄体生成激素释放激素（LHRH）激动剂后，垂体促性腺激素的分泌急剧增加，导致血清睾酮浓度出现短暂升高。这种效应在治疗开始后4至7天达到峰值，5%至10%的患者会出现肿瘤flare的临床症状和体征。
为了确定LHRH诱导的flare反应的影响是否可以预防，在用长效LHRH激动剂醋酸戈舍瑞林（每4周3.6毫克）治疗前，每天给予醋酸环丙孕酮（100毫克）和低剂量己烯雌酚（0.1毫克）4周以抑制垂体。8周后停用己烯雌酚以消除相关的轻微毒性，同时继续给予醋酸环丙孕酮以抑制血管舒缩症状。24名经组织学确诊为前列腺癌的男性纳入研究：6例为C期，2例为D1期，16例为D2期。
导入治疗在1周内将血清睾酮浓度降至去势范围内，给予醋酸戈舍瑞林后平均水平未观察到显著变化。对血清前列腺特异性抗原（PSA）的初始正常化率也没有影响；10周后50%的患者PSA值恢复正常，32周后70%的患者恢复正常。在D2期疾病患者亚组中，治疗32周后血清PSA稳定或下降至正常水平预示着更长的中位生存期。该方案耐受性良好，潮热发生率低。
这些结果表明，在没有LHRH诱导的肿瘤flare的情况下，预后与治疗将PSA最低点维持在正常范围内的能力有关。
