Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei 10016, Taiwan.
Invest New Drugs. 2012 Feb;30(1):282-9. doi: 10.1007/s10637-010-9522-3. Epub 2010 Sep 1.
This phase I study was performed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of an untargeted liposomal formulation of vinorelbine (NanoVNB®) and to characterize its plasma pharmacokinetics in patients with advanced solid tumors which were refractory to conventional treatment or without an effective treatment.
PATIENTS & METHODS: The study incorporated an accelerated titration design. Twenty-two patients with various solid tumors were enrolled. NanoVNB(®) was administered intravenously at doses of 2.2-23 mg/m(2) once every 14 days. Pharmacokinetic endpoints were evaluated in the first cycle. The safety profiles and anti-tumor effects of NanoVNB® were also determined.
Skin rash was the DLT and the most common non-hematological toxicity. The MTD was 18.5 mg/m(2). Drug-related grade 3-4 hematological toxicities were infrequent. Compared with intravenous free vinorelbine, NanoVNB® showed a high C(max) and low plasma clearance. Of the 11 patients completing at least 1 post-treatment tumor assessment, 5 had stable disease. No responders were noted.
NanoVNB® was well tolerated and exhibited more favorable pharmacokinetic profiles than free vinorelbine. Based on dose-limiting skin toxicity, further evaluation of NanoVNB® starting from 18.5 mg/m(2) as a single agent or in combination with other chemotherapeutic agents for vinorelbine-active malignancies is warranted.
本 I 期研究旨在确定长春瑞滨非靶向脂质体（NanoVNB®）的最大耐受剂量（MTD）和剂量限制性毒性（DLT），并描述其在常规治疗耐药或无有效治疗的晚期实体瘤患者中的血浆药代动力学特征。
该研究采用加速滴定设计。共纳入 22 例各种实体瘤患者。NanoVNB（®）以 2.2-23mg/m²的剂量静脉给药，每 14 天一次。在第一个周期中评估药代动力学终点。还确定了 NanoVNB®的安全性特征和抗肿瘤作用。
皮疹是 DLT 和最常见的非血液学毒性。MTD 为 18.5mg/m²。药物相关的 3-4 级血液学毒性不常见。与静脉内游离长春瑞滨相比，NanoVNB®表现出更高的 Cmax 和更低的血浆清除率。在至少完成 1 次治疗后肿瘤评估的 11 例患者中，5 例疾病稳定。未观察到应答者。
NanoVNB®具有良好的耐受性，药代动力学特征优于游离长春瑞滨。基于剂量限制的皮肤毒性，有必要进一步评估 NanoVNB®作为单药或与其他长春瑞滨活性化疗药物联合用于治疗。
