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Metformin as a repurposed therapy in advanced non-small cell lung cancer (NSCLC): results of a phase II trial

  • PHASE II STUDIES
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Summary

Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity. Metformin was initiated at 1000 mg/day for week 1, 1500 mg/day for week 2, then 2000 mg/day thereafter, in divided doses. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and adverse events (AE). Tumor tissue was tested for LKB1/STK11 mutations, and non-fasting serum insulin levels were longitudinally assessed. Results Of a planned 50 patients, 14 were enrolled. ORR was 23% and median PFS was 3.9 months. Median OS was 11.7 months. No LKB1/STK11 mutations were identified. The most common AE were fatigue (42.9%), anemia, and nausea (28.6% each). The most common grade III AE was nausea (14.3%). No grade IV AE occurred. Mean duration of metformin treatment was 5.6 months. Conclusion Adding metformin to chemotherapy for advanced NSCLC was safe but did not significantly improve clinical outcomes compared to historical phase III controls. These results are limited by the small sample size; larger trials are needed.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Mount Sinai Health System, Icahn School of Medicine, Mount Sinai Downtown- Chelsea Cancer Center, 325 W. 15th St, New York, NY, 10011, USA

    Anish B. Parikh, Peter Kozuch & Nicholas Rohs

  2. Manhattan Veterans Association Hospital, NYU Langone Perlmutter Cancer Center, New York, NY, USA

    Daniel J. Becker

  3. Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, Washington, DC, USA

    Benjamin P. Levy

Authors
  1. Anish B. Parikh
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  2. Peter Kozuch
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  3. Nicholas Rohs
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  4. Daniel J. Becker
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Correspondence to Anish B. Parikh.

Ethics declarations

Research Involving Human Participants and/or Animals- 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.

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

Additional information

Suggested Reviewers:

George Simon, MD Anderson, gsimon@mdanderson.org

Bryan Schneider, University of Michigan, bryansch@med.umich.edu.

Martin Edelman, Fox Chase Cancer Center, Martin.edelman@fccc.edu

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Parikh, A.B., Kozuch, P., Rohs, N. et al. Metformin as a repurposed therapy in advanced non-small cell lung cancer (NSCLC): results of a phase II trial. Invest New Drugs 35, 813–819 (2017). https://doi.org/10.1007/s10637-017-0511-7

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  • DOI: https://doi.org/10.1007/s10637-017-0511-7

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