Survival impact and toxicity of metformin in head and neck cancer: An analysis of the SEER-Medicare dataset

Oral Oncol. 2018 Sep:84:12-19. doi: 10.1016/j.oraloncology.2018.06.022. Epub 2018 Jun 30.

Abstract

Objectives: Recent preclinical research has renewed interest in the interplay between glucose dysregulation and cancer. Metformin holds promise as an adjunctive antineoplastic agent in head and neck cancer (HNC). We aimed to explore the impact of metformin in HNC patients from a population-based dataset.

Patients & methods: Patients diagnosed with HNC from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset and categorized into three groups: non-diabetics (nD), diabetics not taking metformin (DnM), and diabetics taking metformin (D + M). Overall survival (OS) and cancer-specific survival (CSS) were compared between groups using Kaplan-Meier and Cox regression controlling for sociodemographic, clinical, and treatment covariates. The incidence of toxicities associated with HNC therapy was compared among groups using χ2 analysis.

Results: Among 1646 patients, there were 1144 nD, 378 DnM, and 124 D + M. 2-year OS rates was 65.6% for nD, 57.7% for DnM, and 73.4% for D + M by Kaplan-Meier (p < 0.01), and corresponding rates of 2-year CSS were 73.7%, 66.1%, and 88.8% (p < 0.01), respectively. On Cox multivariable analysis, OS among the three groups did not significantly differ; however, CSS was significantly worse among both nD versus DnM as compared to D + M. Toxicity rates were not significantly increased among D + M.

Conclusion: HNC patients with diabetes taking metformin experience improved CSS. Prospective investigation of the addition of metformin to standard-of-care HNC therapy is warranted.

Keywords: Diabetes; Head and neck cancer; Metformin; Warburg effect.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticholesteremic Agents / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Cohort Studies
  • Combined Modality Therapy
  • Diabetes Mellitus / drug therapy*
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy
  • Female
  • Head and Neck Neoplasms / complications
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypertension / drug therapy
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Proportional Hazards Models
  • Registries
  • SEER Program
  • Socioeconomic Factors
  • Squamous Cell Carcinoma of Head and Neck / complications
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / therapy
  • United States / epidemiology

Substances

  • Anticholesteremic Agents
  • Antihypertensive Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypoglycemic Agents
  • Metformin