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Apatinib, a novel VEGFR inhibitor plus docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR: a phase I trial

  • Jian-Chun Duan
  • Zhi-Jie Wang
  • Lin Lin
  • Jun-Ling Li
  • Yan Wang
  • Hua Bai
  • Xing-Sheng Hu
  • Yu-Tao Liu
  • Xue-Zhi Hao
  • Hong-Yu Wang
  • Rui Wan
  • Xin Wang
  • Jie WangEmail author
PHASE I STUDIES
  • 111 Downloads

Summary

Background This phase I trial was primarily conducted to determine the maximum tolerated dose (MTD) of apatinib combined with docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR who have failed to first-line platinum-based chemotherapy, and to evaluate the safety and tolerability of apatinib plus docetaxel. Methods This was a single-center, open-label, dose-escalating phase I trial. The study used a standard 3 + 3 dose escalation design with the primary aim of determining the MTD. Twelve patients with advanced lung adenocarcinoma were enrolled, the primary endpoint was safety. Two doses of apatinib, 250 mg/day (level 1) and 500 mg/day (level 2), were evaluated in combination with 60 mg/m2 doxetacel every 3 weeks. Six patients have been treated at levels 1 and 2, respectively. Optimal dose of apatinib was determined by dose-limiting toxicity (DLT). Results Six patients have been treated at levels 1 and 2. At level 1, one of six patients experienced grade 3 acneiform rash as DLTs. At level 2, two patients experienced grade 3 hypertension and one experienced grade 3 nasal bleeding. MTD and recommended dose for phase II study was 250 mg/day. Most frequent adverse events of any grade were bilirubin elevation, hypertension, alanine aminotransferase elevation, transglutaminase elevation, hand foot syndrome and fatigue. The median progression-free survival was 2.76 month. Moreover, three patients had developed progressive disease and the mean duration of response was 2.79 months. Conclusion Apatinib plus docetaxel was well tolerated and showed promising efficacy in advanced lung adenocarcinoma. This combination therapy may represent a potent therapeutic option for advanced lung adenocarcinoma patients with wild-type EGFR.

Keywords

Apatinib Docetaxel Lung adenocarcinoma Wild-type EGFR 

Notes

Acknowledgements

We would like to thank Jiangsu HengRui Medicine Co., Ltd. for supporting our research. And we thank all participants and their families.

Funding

This research was supported by Jiangsu HengRui Medicine Co., Ltd., and CAMS Innovation Fund for Medical Sciences (CIFMS) [number: 2017-12M-005].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jian-Chun Duan
    • 1
  • Zhi-Jie Wang
    • 1
  • Lin Lin
    • 1
  • Jun-Ling Li
    • 1
  • Yan Wang
    • 1
  • Hua Bai
    • 1
  • Xing-Sheng Hu
    • 1
  • Yu-Tao Liu
    • 1
  • Xue-Zhi Hao
    • 1
  • Hong-Yu Wang
    • 1
  • Rui Wan
    • 1
  • Xin Wang
    • 1
  • Jie Wang
    • 1
    Email author
  1. 1.State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center and Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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