Harris K A, Reese D M
Urologic Oncology Program, Department of Medicine, UCSF Comprehensive Cancer Center, University of California, San Francisco, USA.
Drugs. 2001;61(15):2177-92. doi: 10.2165/00003495-200161150-00003.
Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases will develop disease progression. Patients with hormone refractory prostate cancer (HRPC) have a median survival of approximately 18 months and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone. Until recently, cytotoxic chemotherapy was felt to be relatively ineffective in the treatment of HRPC. Combination regimens incorporating new active agents have demonstrated significant activity in this setting, renewing interest in the use of chemotherapy to treat HRPC. Recent advances in the understanding of prostate cancer biology have led to the development of drugs directed against precise molecular alterations in the prostate tumour cell. Biologic agents now in development include those capable of altering signal transduction, blocking angiogenesis, inhibiting cell cycle progression, and stimulating apoptosis. In addition, many types of immune therapies are showing promise. Evaluating these agents, and incorporating them into existing regimens, are major goals of ongoing clinical research in advanced prostate cancer.
前列腺癌是西方国家男性癌症死亡的第二大主要原因。晚期前列腺癌的初始治疗是通过药物或手术去势抑制睾丸雄激素的产生，但几乎所有发生转移的男性都会出现疾病进展。激素难治性前列腺癌（HRPC）患者的中位生存期约为18个月，尚无治疗方法显示出明确的生存优势。然而，在过去几年中，出现了一些有前景的新治疗策略。最重要的新治疗策略之一是在初始雄激素剥夺治疗失败后进行二次激素调控。这种方法基于这样的认识，即HRPC是一种异质性疾病，尽管睾酮水平处于去势水平，但一些患者可能对替代激素干预有反应。直到最近，细胞毒性化疗在HRPC治疗中仍被认为相对无效。包含新活性药物的联合方案在这种情况下已显示出显著活性，重新引发了对使用化疗治疗HRPC的兴趣。对前列腺癌生物学认识的最新进展导致了针对前列腺肿瘤细胞精确分子改变的药物的开发。目前正在研发的生物制剂包括能够改变信号转导、阻断血管生成、抑制细胞周期进程和刺激细胞凋亡的制剂。此外，许多类型的免疫疗法也显示出前景。评估这些药物并将它们纳入现有治疗方案是晚期前列腺癌正在进行的临床研究的主要目标。
