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Invest New Drugs. 2018 Jun;36(3):435-441. doi: 10.1007/s10637-017-0515-3. Epub 2017 Oct 2.

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

Author information

1
Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA. Priyanka.bhateja@uhhospitals.org.
2
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA. Priyanka.bhateja@uhhospitals.org.
3
Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA.
4
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA.
5
Novartis Institute of Biomedical Research, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936-1080, USA.

Abstract

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.

KEYWORDS:

Erlotinib; NF-KB; Non small cell lung cancer; Phase I; Quinacrine

PMID:
28971268
DOI:
10.1007/s10637-017-0515-3

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