Phase I clinical trial to determine maximum tolerated dose of oral albendazole in patients with advanced cancer
Phase I clinical trial to determine maximum tolerated dose of oral albendazole in patients with advanced cancer
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DOI：
10.1007/s00280-009-1157-8
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发表时间：
2010-02-01
影响因子：
3
通讯作者：
Links, Matthew
中科院分区：
文献类型：
--
作者：
Pourgholami, Mohammad H.;Szwajcer, Michael;Links, Matthew
阿苯达唑是一种潜在的抗癌药物，目前正在开发中，用于治疗癌症。我们对晚期恶性肿瘤患者进行了口服阿苯达唑的I期剂量发现研究。36例难治性实体瘤患者入选。阿苯达唑在3周周期的第1-14天口服，从400 mg bd开始，剂量递增至1200 mg bd。连续采血至96h，第1、4周期第8天采血，最大耐受量为每天2400 mg(1200bd)。骨髓抑制是主要的剂量限制性毒性。疲劳和轻微的胃肠道不适是其他主要不良反应。在24例可评估的患者中，4例(16%)有肿瘤标志物反应，较基线值下降至少50%，1例患者有较长时间的稳定标记物反应。观察到血浆血管内皮生长因子水平下降。阿苯达唑在本试验测试的方案中耐受性良好。这项研究的结果表明，进一步研究的推荐剂量为1,200毫克，每天两次，连续14天，21天为一周期。
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.