Investigational New Drugs

, Volume 36, Issue 2, pp 269–277 | Cite as

Phase I dose escalation and pharmacokinetic study on the nanoparticle formulation of polymeric micellar paclitaxel for injection in patients with advanced solid malignancies

  • Meiqi Shi
  • Jing Sun
  • Jinsong Zhou
  • Hao Yu
  • Shaorong Yu
  • Guohao Xia
  • Li Wang
  • Yue Teng
  • Gangyi Liu
  • Chen Yu
  • Jifeng Feng
  • Yaling Shen
PHASE I STUDIES
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Summary

Background Polymeric micellar paclitaxel (PM-paclitaxel) is a novel Cremophor EL-free, nanoparticle-encapsulated paclitaxel formulation administered through intravenous injection. The primary objective of this phase I trial was to determine the first cycle dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PM-paclitaxel. Secondary objectives included the evaluation of the safety, antitumor activity, and pharmacokinetic (PK) profile of PM-paclitaxel in patients with advanced malignancies. Methods The PM-paclitaxel dose was escalated from 175 mg/m2 (level 1) to 435 mg/m2 (level 5). PM-paclitaxel was intravenously administered to patients for 3 h without premedication on day 1 of a 21-day cycle. Results Eighteen patients with confirmed advanced malignancies received PM-paclitaxel. DLT included grade 4 neutropenia (four patients) and grade 3 numbness (one patient), which occurred in one of the six patients who received 300 mg/m2 (level 3) PM-paclitaxel and all three patients who were treated with 435 mg/m2 PM-paclitaxel. Thus, the MTD of PM-paclitaxel was determined as 390 mg/m2 (level 4). Acute hypersensitive reactions were not observed. Partial response was observed in six of 18 patients (33.3%), three of whom had prior exposure to paclitaxel chemotherapy. The peak concentration and area under the curve values of paclitaxel increased with increasing dosage, indicating that PM-paclitaxel exhibits linear PKs. Conclusions PM-paclitaxel showed high MTD without additional toxicity, and exhibited desirable antitumor activity. The recommended dose of PM paclitaxel for phase II study is 300 mg/m2.

Keywords

Phase I Paclitaxel Nanoparticle Polymeric micelle Solid malignancies 

Notes

Acknowledgements

The authors thank the patients who participated in this study and express appreciation of the assistance and understanding of their families. The authors also thank the study-site staff for their support.

Funding

The work was also supported by trial funding provided by Ministry of Science and Technology of the People’s Republic of China (grant number 14C26213100947) and science and Technology Commission of Shanghai Municipality (grant number 14431908600).

Compliance with ethical standards

Conflict of interest

All authors received research funding from Shanghai Yizhong Biotechnical Co., Ltd., China for conducting the study and preparing this report. No potential conflicts of interest were disclosed.

Ethical approval

The study was approved by the institutional review board of the Jiangsu Cancer Hospital, Nanjing, China. The study was conducted in compliance with the ethical principles originating in the Declaration of Helsinki.

Informed consent

Written informed consent was obtained from all individual patients included in the study.

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Copyright information

© Springer Science+Business Media, LLC 2017
Corrected publication September/2017

Authors and Affiliations

  • Meiqi Shi
    • 1
  • Jing Sun
    • 2
    • 3
  • Jinsong Zhou
    • 3
  • Hao Yu
    • 4
  • Shaorong Yu
    • 1
  • Guohao Xia
    • 1
  • Li Wang
    • 1
  • Yue Teng
    • 1
  • Gangyi Liu
    • 5
  • Chen Yu
    • 5
  • Jifeng Feng
    • 1
  • Yaling Shen
    • 2
    • 3
  1. 1.Department of OncologyAffiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer ResearchNanjingChina
  2. 2.State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing TechnologyEast China University of Science & Technology ChinaShanghaiChina
  3. 3.Shanghai Yizhong Biotechnical Co., Ltd.ShanghaiChina
  4. 4.Department of BiostatisticsSchool of Public Health Nanjing Medical UniversityNanjingChina
  5. 5.Central LaboratoryShanghai Xuhui Central HospitalShanghaiChina

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