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Phase I study of the combination of quinacrine and erlotinib in patients with locally advanced or metastatic non small cell lung cancer

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Summary

Introduction Preclinical data suggest quinacrine acts as an inhibitor of FACT (facilitates chromatin transcription) complex, which may play a role in TKI (tyrosine kinase inhibitor) resistance. The aim of this Phase I study was to study the safety and assess the maximum tolerated dose of quinacrine in combination with erlotinib in non small cell lung cancer (NSCLC). Methods This was a phase I study with standard 3 + 3 dose escalation design with the primary aim of determining the maximum tolerated dose. Two of 3 patients enrolled at dose level 1 experienced dose limiting toxicity (DLT). The next 6 patients were enrolled at dose level − 1 and none of these 6 patients experienced DLT. The dose of 50 mg of quinacrine every other day with 150 mg of erlotinib was established as the maximum tolerated and the recommended phase II dose. One of 3 patients treated at dose level 1 had stable disease. One of 6 patients treated at dose level − 1 had partial response for 6 months, the rest had progressive disease at the time of first assessment. Conclusion Combination of quinacrine and erlotinib was well tolerated but showed limited efficacy in advanced NSCLC.

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Funding

This study was funded by the Case Comprehensive Cancer Center’s Early Phase Clinical Research Support and University Hospital Cleveland Medical Center. Quinacrine was provided by Incuron.

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Authors and Affiliations

  1. Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA

    Priyanka Bhateja & Afshin Dowlati

  2. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA

    Priyanka Bhateja & Afshin Dowlati

  3. Novartis Institute of Biomedical Research, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936-1080, USA

    Neelesh Sharma

Authors
  1. Priyanka Bhateja
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  2. Afshin Dowlati
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  3. Neelesh Sharma
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Corresponding author

Correspondence to Priyanka Bhateja.

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Conflict of interest

Afshin Dowlati received research grants from Bristol-Myers Squibb, Abbvie, AstraZeneca, Novartis Pharma and Roche-Peru and consulting role for Ariad pharmaceuticals. Neelesh Sharma received research funding from Incuron during the study and is currently employed by Novartis Pharma. Priyanka Bhateja declares that she has no conflicts 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. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.

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Bhateja, P., Dowlati, A. & Sharma, N. Phase I study of the combination of quinacrine and erlotinib in patients with locally advanced or metastatic non small cell lung cancer. Invest New Drugs 36, 435–441 (2018). https://doi.org/10.1007/s10637-017-0515-3

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  • DOI: https://doi.org/10.1007/s10637-017-0515-3

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