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A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor

  • PHASE I STUDIES
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Summary

Purpose 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/m2 once every 14 days. Pharmacokinetic endpoints were evaluated in the first cycle. The safety profiles and anti-tumor effects of NanoVNB® were also determined. Results Skin rash was the DLT and the most common non-hematological toxicity. The MTD was 18.5 mg/m2. Drug-related grade 3–4 hematological toxicities were infrequent. Compared with intravenous free vinorelbine, NanoVNB® showed a high Cmax and low plasma clearance. Of the 11 patients completing at least 1 post-treatment tumor assessment, 5 had stable disease. No responders were noted. Conclusion 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/m2 as a single agent or in combination with other chemotherapeutic agents for vinorelbine-active malignancies is warranted.

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Acknowledgments

This work was supported by Taiwan Liposome Co., Ltd. (Taipei, Taiwan).

Conflict of interest statement

No financial or other potential conflicts of interest exist for any of the authors.

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Authors and Affiliations

  1. Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei, 10016, Taiwan

    Shih-Hung Yang, Chia-Chi Lin, Zhong-Zhe Lin & Ruey-Long Hong

  2. Department of Oncology, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan

    Shih-Hung Yang & Zhong-Zhe Lin

  3. Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan

    Chia-Chi Lin, Zhong-Zhe Lin & Ruey-Long Hong

  4. Taiwan Liposome Company, Ltd, Taipei, Taiwan

    Yun-Long Tseng

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  1. Shih-Hung Yang
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  2. Chia-Chi Lin
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Correspondence to Ruey-Long Hong.

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Yang, SH., Lin, CC., Lin, ZZ. et al. A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor. Invest New Drugs 30, 282–289 (2012). https://doi.org/10.1007/s10637-010-9522-3

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  • DOI: https://doi.org/10.1007/s10637-010-9522-3

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