Cancer Pharmacology and Therapeutics, St George Hospital Cancer Care, and Department of Surgery, St George Clinical School, University of New South Wales, Sydney, Australia.
Cancer Chemother Pharmacol. 2010 Feb;65(3):597-605. doi: 10.1007/s00280-009-1157-8.
Albendazole is a potential anticancer agent that is currently under development for the treatment of cancer. We carried out a dose-finding phase I study of oral albendazole in patients with advanced malignancies.
Thirty-six patients with refractory solid tumors were enrolled. Albendazole was given orally on a day 1-14 of a 3 weekly cycle, starting at 400 mg BD with dose escalation until 1,200 mg BD. Serial blood samples were collected up to 96 h and also on day 8 of cycles 1 and 4.
The maximum tolerated dose was 2,400 mg per day (1,200 BD). Myelosuppression was the main dose limiting toxicity. Fatigue and mild gastrointestinal upset were the other major adverse effects. 4 out of 24 assessable patients (16%) had a tumor marker response with a fall of at least 50% from baseline values and another patient had a prolonged period of stable marker response. A decline in plasma vascular endothelial growth factor levels was observed.
Albendazole was well tolerated on the schedule tested in this trial. The results of this study suggest that the recommended dose for further study is 1,200 mg twice daily for 14 days in a 21-day cycle.
阿苯达唑是一种有潜力的抗癌药物，目前正在开发用于癌症治疗。我们对晚期恶性肿瘤患者进行了口服阿苯达唑的剂量探索 I 期研究。
共纳入 36 例难治性实体瘤患者。阿苯达唑于每 3 周的第 1-14 天口服，起始剂量为 400mg，每日 2 次（BD），剂量递增至 1,200mg BD。在 96 小时内和第 1 周期和第 4 周期的第 8 天采集连续血样。
最大耐受剂量为每天 2,400mg（1,200 BD）。骨髓抑制是主要的剂量限制毒性。疲劳和轻度胃肠道不适是其他主要不良反应。24 例可评估患者中有 4 例（16%）出现肿瘤标志物应答，与基线值相比至少下降 50%，另有 1 例患者出现标志物应答的稳定期延长。观察到血浆血管内皮生长因子水平下降。
在本试验中测试的方案中，阿苯达唑耐受良好。本研究结果表明，进一步研究的推荐剂量为每 21 天周期中，1,200mg 每日 2 次，连用 14 天。
