Scher H I, Liebertz C, Kelly W K, Mazumdar M, Brett C, Schwartz L, Kolvenbag G, Shapiro L, Schwartz M
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 1997 Aug;15(8):2928-38. doi: 10.1200/JCO.1997.15.8.2928.
To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities.
Patients with progressive prostate cancer were treated with bicalutamide 200 mg daily. Before treatment, patients' tumors were classified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups. Prior exposure to flutamide and response to flutamide withdrawal was also considered. Outcomes were reported independently on the basis of posttherapy changes in prostate-specific antigen (PSA), measurable disease, and radionuclide bone scans.
Outcomes varied by prior hormone exposure as a higher proportion of patients with progression of androgen-dependent tumors showed posttherapy PSA decreases of more than 50% or more than 80%, measurable disease regression, and improvement on radionuclide bone scans than did patients with androgen-independent progression. Within the category of androgen-independent progression, clinical benefit was observed in patients who had previously progressed on flutamide, independent of the response to flutamide withdrawal. Patients who had progressed on a gonadotropin-releasing hormone (GnRH) analog alone had a low response proportion, whereas those who progressed after two or more hormone therapies did not respond. Overall, the drug was well tolerated. After progression on bicalutamide monotherapy, one third of patients with androgen-dependent progression responded to medical castration with a GnRH analog.
Classifying patient tumors on the basis of prior hormone exposure permits a more precise estimate of the potential benefit of a specific hormone therapy for the individual patient. The precision is further increased by reporting the effects of a drug on each parameter of disease independently. The difference in outcomes for patients with androgen-independent progression suggests that the specific hormone therapy administered and the response to that therapy can influence the biology of the relapsing tumor and the sensitivity to subsequent therapies. The sensitivity to bicalutamide after progression on flutamide deserves further study.
确定200毫克比卡鲁胺对不同激素敏感性前列腺癌患者的治疗效果。
对进展期前列腺癌患者每日给予200毫克比卡鲁胺治疗。治疗前，根据既往激素暴露情况和血清睾酮水平将患者肿瘤分为雄激素依赖性和雄激素非依赖性组。还考虑了既往氟他胺暴露情况及对氟他胺撤药的反应。根据治疗后前列腺特异性抗原（PSA）变化、可测量疾病及放射性核素骨扫描情况独立报告结果。
结果因既往激素暴露情况而异，与雄激素非依赖性进展患者相比，雄激素依赖性肿瘤进展患者中，更高比例的患者治疗后PSA下降超过50%或超过80%，可测量疾病消退，放射性核素骨扫描改善。在雄激素非依赖性进展类别中，既往在氟他胺治疗中进展的患者观察到临床获益，与对氟他胺撤药的反应无关。仅在促性腺激素释放激素（GnRH）类似物治疗中进展的患者反应比例较低，而在接受两种或更多激素治疗后进展的患者无反应。总体而言，该药物耐受性良好。比卡鲁胺单药治疗进展后，三分之一雄激素依赖性进展患者对GnRH类似物药物去势治疗有反应。
根据既往激素暴露情况对患者肿瘤进行分类，可更精确地估计特定激素治疗对个体患者的潜在益处。通过独立报告药物对疾病各参数的影响，可进一步提高精确性。雄激素非依赖性进展患者结果的差异表明，所给予特定激素治疗及其对该治疗的反应可影响复发性肿瘤生物学特性及对后续治疗的敏感性。氟他胺治疗进展后对比卡鲁胺的敏感性值得进一步研究。
