Scher H I, Steineck G, Kelly W K
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Urology. 1995 Aug;46(2):142-8. doi: 10.1016/s0090-4295(99)80182-4.
A wide range of responses have been reported to second-line hormonal therapies, including corticosteroids and the withdrawal of antiandrogens in patients with hormone-refractory prostate cancers. This suggested the need to classify patients on the basis of hormonal sensitivity. A schema was developed by assessing the differences in entry criteria in relation to outcomes for clinical protocols with hydrocortisone alone or in combination with other agents for patients who had progressed after primary hormone therapy.
Published clinical trials of patients who had progressed after primary hormone treatment, which included glucocorticoids, were retrieved from Medline listings. The trials included patients treated with hydrocortisone alone, hydrocortisone and aminoglutethimide, hydrocortisone plus suramin, dexamethasone, and prednisone alone or in combination with chemotherapy.
The definitions used for refractory disease ranged from none, to "progression", to "unsuccessful second medical or surgical castration. "None of the trials included a definition for hormone-refractory disease based on objective criteria. Details were lacking on most trials with respect to the response to and specific types of hormonal therapies. Furthermore, few trials controlled for the potential contribution of the "flutamide withdrawal syndrome" on outcome.
The term "hormone-refractory" prostate cancer has evolved to include patients with a spectrum of diseases. As utilized in clinical trials of second-line hormonal therapies, patients who have received one and as many as six different treatments have been included in the same study. A new classification of patients based on hormonal sensitivity is proposed to recognize that androgen-independent proliferation, progression of disease despite castrate levels of testosterone, does not necessarily mean that a tumor is refractory to hormonal manipulations. Future trials in hormonally relapsed patients must include more details of the hormonal therapies utilized.
对于二线激素疗法，包括皮质类固醇以及激素难治性前列腺癌患者停用抗雄激素药物，已有广泛的反应报道。这表明有必要根据激素敏感性对患者进行分类。通过评估仅使用氢化可的松或与其他药物联合用于一线激素治疗后病情进展患者的临床方案的入组标准差异，制定了一种方案。
从Medline列表中检索已发表的关于一线激素治疗后病情进展患者的临床试验，这些试验包括糖皮质激素。试验包括单独使用氢化可的松、氢化可的松与氨鲁米特、氢化可的松加苏拉明、地塞米松、泼尼松单独或与化疗联合治疗的患者。
难治性疾病的定义范围从无到“进展”，再到“二次药物或手术去势失败”。没有一项试验包含基于客观标准的激素难治性疾病定义。大多数试验缺乏关于激素治疗反应和具体类型的详细信息。此外，很少有试验控制“氟他胺撤药综合征”对结果的潜在影响。
“激素难治性”前列腺癌这一术语已演变为包括一系列疾病的患者。在二线激素治疗的临床试验中，接受过一种乃至六种不同治疗的患者被纳入了同一研究。建议根据激素敏感性对患者进行新的分类，以认识到雄激素非依赖性增殖，即尽管睾酮处于去势水平但疾病仍进展，并不一定意味着肿瘤对激素操纵难治。未来针对激素复发患者的试验必须包括所采用激素治疗的更多详细信息。
