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Metformin Use During Treatment of Potentially Curable Esophageal Cancer Patients is not Associated with Better Outcomes

Annals of Surgical Oncology volume 22, pages 766–771 (2015)Cite this article

Abstract

Background

Metformin use has been associated with a dose-dependent increased response to neoadjuvant chemo(radio)therapy in esophageal cancer patients. However, no association between metformin use and overall survival has been reported yet. The purpose of our study was to investigate the effect of metformin use on pathological response as well as overall and disease-free survival in patients with resectable esophageal cancer.

Methods

Between March 1994 and September 2013, all patients undergoing an esophagectomy for esophageal and gastroesophageal junction cancer after neoadjuvant chemo(radio)therapy with curative intent were included in a prospective database. A complete pathological response was defined as ypT0N0M0, Mandard 1. Kaplan–Meier curves with log-rank testing were performed for overall survival and disease-free survival.

Results

A total of 461 patients were included with a median follow-up of 24 months (range 1–228); 43 patients were diagnosed with diabetes mellitus type II (9.3 %) of whom 32 patients used metformin (74 %). A total of 94 (20 %) patients had a complete pathological response, which did not differ between metformin users (19 %) and non-metformin users (21 %, p = 0.99). We did not observe a statistically significant difference between metformin users and non-metformin users for median overall survival (43.6 vs. 42.8 months, p = 0.66) or for median disease-free survival (31.1 vs. 47.0 months, p = 0.68). A subgroup analysis in patients with diabetes mellitus type II showed a nonsignificant increase in median overall survival for metformin users (43.6 months) compared with non-metformin users (21.4 months, p = 0.44). For median disease-free survival, a similar nonsignificant increase was observed for metformin users (31.1 months) compared with non-metformin users (20.1 months, p = 0.31).

Conclusions

The use of metformin did not result in higher pathological response rates or improved overall survival or disease-free survival compared with non-metformin use in patients receiving neoadjuvant chemo(radio)therapy for resectable esophageal cancer. In contrast to what has been postulated for other tumor types, metformin may not have a beneficial effect in esophageal cancer.

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Acknowledgement

SM Lagarde is supported by a Koningin Wilhelmina Fonds (KWF, Dutch Cancer Society) Fellowship, UVA 2013-5853.

Conflict of interest

None reported.

Author information

Affiliations

  1. Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands

    L. E. A. M. M. Spierings MD, M. G. H. van Oijen PhD, J. W. Wilmink MD, PhD & H. W. M. van Laarhoven MD, PhD

  2. Department of Surgical Oncology, Academic Medical Centre, Amsterdam, The Netherlands

    S. M. Lagarde MD, PhD, S. S. Gisbertz MD, PhD, M. C. Anderegg MD & M. I. van Berge Henegouwen MD, PhD

  3. Department of Radiation Oncology, Academic Medical Centre, Amsterdam, The Netherlands

    M. C. C. M. Hulshof MD, PhD

  4. Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands

    S. L. Meijer MD, PhD

Authors
  1. L. E. A. M. M. Spierings MD
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  2. S. M. Lagarde MD, PhD
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  3. M. G. H. van Oijen PhD
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  4. S. S. Gisbertz MD, PhD
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  5. J. W. Wilmink MD, PhD
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  6. M. C. C. M. Hulshof MD, PhD
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  7. S. L. Meijer MD, PhD
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  8. M. C. Anderegg MD
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  9. M. I. van Berge Henegouwen MD, PhD
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  10. H. W. M. van Laarhoven MD, PhD
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Corresponding author

Correspondence to H. W. M. van Laarhoven MD, PhD.

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Spierings, L.E.A.M.M., Lagarde, S.M., van Oijen, M.G.H. et al. Metformin Use During Treatment of Potentially Curable Esophageal Cancer Patients is not Associated with Better Outcomes. Ann Surg Oncol 22, 766–771 (2015). https://doi.org/10.1245/s10434-015-4850-3

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  • DOI: https://doi.org/10.1245/s10434-015-4850-3

Keywords

  • Diabetes Mellitus Type
  • Metformin
  • Esophageal Cancer
  • Pathological Response
  • Complete Pathological Response