Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer
Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer
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DOI：
10.1007/s00280-007-0665-7
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发表时间：
2008-06-01
影响因子：
3
通讯作者：
Bodrogi, I.
中科院分区：
文献类型：
--
作者：
Horti, J.;Juhasz, E.;Bodrogi, I.
目的本I期研究的目的是评价TZT-1027的最大耐受剂量（MTD）、剂量限制性毒性（DLT）、II期研究的推荐剂量、药代动力学和抗肿瘤活性当每3-4周施用时，在患有非小细胞肺癌（NSCLC）的患者中使用索毕多汀（soblidotin）。常规治疗难治或无标准治疗可用的III/B或IV期NSCLC;东部肿瘤协作组（ECOG）体力状态（PS）= 20且< 75岁。患者接受TZT-1027给药，剂量从0.5 mg/m2递增至5.6 mg/m2。在每个疗程中采集药代动力学样本。3例患者发生DLT，包括中性粒细胞减少症、中性粒细胞减少症并发发热、肌痛和神经性疼痛。常见毒副反应包括便秘、厌食、脱发、恶心、白细胞减少和中性粒细胞减少。观察到1例完全缓解和3例部分缓解。TZT-1027的药代动力学参数（AUC和C（max））随剂量增加呈线性增加趋势。结论DLT包括中性粒细胞减少、中性粒细胞减少伴发热、肌痛和神经病理性疼痛。MTD为4.8 mg/m2。TZT-1027的II期研究推荐剂量为4.8 mg/m2，每3-4周一次。
Purpose The purpose of this phase I study was to evaluate the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), the recommended dose for phase II study, pharmacokinetics, and antitumor activity of TZT-1027 (soblidotin) in patients with non-small cell lung cancer (NSCLC) when administered every 3-4 weeks.Methods Eligible patients had the following characteristics: stage III/b or IV NSCLC that was refractory to conventional therapy or for which no standard therapy was available; Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 20 and < 75 years. The patients were administered TZT-1027 in escalating doses from 0.5 to 5.6 mg/m(2). Pharmacokinetic samples were collected during each treatment course.Results Forty-nine patients were enrolled. Three patients had DLTs, including neutropenia, neutropenia complicated by fever, myalgia, and neuropathic pain. The common toxicities included constipation, anorexia, alopecia, nausea, leukopenia, and neutropenia. One complete response and three partial responses were observed. The pharmacokinetic parameters (AUC and C (max)) of TZT-1027 tended to increase linearly with dose.Conclusions DLTs included neutropenia, neutropenia complicated by fever, myalgia, and neuropathic pain. The MTD was 4.8 mg/m(2). The recommended phase II study dose of TZT-1027 is 4.8 mg/m(2) administered every 3-4 weeks.