Ngo Lynette S M, Yeo Angeline, Wong Alvin S C, Tay Miah Hiang
Department of Medical Oncology, National Cancer Centre, Singapore.
Ann Acad Med Singap. 2007 Oct;36(10):811-4.
The advent of prostate specific antigen (PSA) has resulted in an increased incidence of early detection of prostate cancer recurrence. Patients treated with androgen deprivation therapy (ADT) become hormone-resistant after 18 to 24 months. In patients with biochemical failure, where there is a rise in PSA but no objective evidence of metastases, or in whom there are small volume metastases but who are asymptomatic, there is no standard of care after ADT. Ketoconazole, an antimycotic which affects the synthesis of androgens and other steroids, has shown direct cytotoxic effects in prostate cancer cell lines in in-vitro studies. This study describes our experience with ketoconazole treatment for hormone refractory prostate cancer (HRPC).
A retrospective study of HRPC patients given ketoconazole at the National Cancer Centre and The Cancer Institute from 2004 to 2005 was performed. All eligible patients had histologically proven adenocarcinoma of the prostate and a rising PSA level despite ADT with orchidectomy or luteinising hormone-releasing hormone (LHRH) agonist therapy. All patients received 200 mg of ketoconazole thrice daily. Response was defined as a decline in PSA of at least 50% from the pre-treatment level and confirmed by a second PSA value 4 or more weeks later. The endpoints evaluated were the presence and duration of a response and the toxicity profile of the treatment.
A total of 32 patients with HRPC were treated with ketoconazole. Twelve (38%) of the 32 patients had a greater than 50% decrease in their PSA values. The median duration of response was 6.75 months. The median time to reach PSA nadir was 3.5 months. Five patients continue to exhibit progression-free response at the time of writing. Ketoconazole was generally well tolerated. Eighteen (56%) patients recorded mild toxicities related to ketoconazole. There were no grade 3 or 4 toxicities.
Low-dose ketoconazole bridges the gap in the continuum of treatment for patients who have failed ADT and in whom cytotoxic chemotherapy would have a significant impact on the quality of life. Its good toxicity profile, low cost and ease of administration makes it a viable option for this group of patients.
前列腺特异性抗原（PSA）的出现使得前列腺癌复发的早期检测率有所提高。接受雄激素剥夺疗法（ADT）的患者在18至24个月后会产生激素抵抗。在生化指标失败的患者中，即PSA升高但无转移的客观证据，或存在少量转移灶但无症状的患者，ADT后尚无标准治疗方案。酮康唑是一种抗真菌药，可影响雄激素和其他类固醇的合成，在体外研究中已显示出对前列腺癌细胞系有直接细胞毒性作用。本研究描述了我们使用酮康唑治疗激素难治性前列腺癌（HRPC）的经验。
对2004年至2005年在国家癌症中心和癌症研究所接受酮康唑治疗的HRPC患者进行回顾性研究。所有符合条件的患者均经组织学证实为前列腺腺癌，尽管接受了睾丸切除术或促黄体生成素释放激素（LHRH）激动剂治疗，但PSA水平仍在上升。所有患者每日三次服用200毫克酮康唑。缓解定义为PSA较治疗前水平下降至少50%，并在4周或更长时间后通过第二次PSA值得到确认。评估的终点指标为缓解的存在和持续时间以及治疗的毒性特征。
共有32例HRPC患者接受了酮康唑治疗。32例患者中有12例（38%）的PSA值下降超过50%。缓解的中位持续时间为6.75个月。达到PSA最低点的中位时间为3.5个月。在撰写本文时，有5例患者仍表现为无进展缓解。酮康唑总体耐受性良好。18例（56%）患者记录了与酮康唑相关的轻度毒性。无3级或4级毒性。
低剂量酮康唑填补了ADT失败且细胞毒性化疗会对生活质量产生重大影响的患者连续治疗中的空白。其良好的毒性特征、低成本和易于给药使其成为这类患者的可行选择。
