(P065) Metformin Use Does Not Affect Chemoradiotherapy-Associated Toxicity

S.A. McAvoy, MD, H.E. Soh, BS, R. Komaki, MD, J.D. Cox, MD, J.W. Welsh, MD, T.M. Guerrero, MD, PhD, H.D. Skinner, MD, PhD; UT MD Anderson Cancer Center

Introduction: Recent data suggest that metformin is a potent radiosensitizer in vitro and in vivo. Additionally, metformin use is associated with improved response to chemoradiotherapy in multiple tumor types. Based on these data, clinical trials incorporating metformin and radiotherapy are currently in development. However, the effects of metformin on chemoradiotherapy-associated toxicity are unclear. In the current study, we retrospectively examined two separate patient populations treated with concurrent chemoradiation and examined the effects of metformin treatment on toxicity. Both cohorts are known to exhibit improved outcome in patients taking metformin compared with other methods of glucose control.[1,2]

Methods: The charts of diabetic patients treated with concurrent chemoradiation for either locally advanced esophageal adenocarcinoma (EC) (n = 49) or non–small-cell lung cancer (NSCLC) (n = 62) were retrospectively evaluated for chemoradiotherapy-associated toxicity. Toxicities were scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). The following toxicities were included: acute esophagitis, acute and subacute pneumonitis, nonpneumonitis severe pulmonary complications grade ≥ 3 (pneumonia, pleural effusion, pneumothorax, atelectasis, and acute respiratory failure), and severe cardiac complications grade ≥ 3 in the subacute or chronic setting (arrhythmias, congestive heart failure, and myocardial infarction). Symptomatic esophagitis was defined as grade ≥ 2 requiring new or increased use of narcotics. Cohorts were compared using chi-square statistical analysis.

Results: In NSCLC, no significant differences were observed in symptomatic pneumonitis or esophagitis between patients taking metformin (28% and 50%, respectively) and patients using other methods for glycemic control (23% and 53%; P = .68 and P = .77, respectively). In EC patients, only seven cases of symptomatic pneumonitis were observed. However, no significant differences were observed in symptomatic esophagitis between patients taking metformin (48.3%) and those using other methods of glycemic control (30%; P = .2). No association between metformin dose (0–1,500 mg/d vs ≥ 1,500 mg/d) and symptomatic esophagitis was observed (P = .19). EC patients taking metformin had significantly fewer nonpneumonitis severe pulmonary complications (17.2% vs 50%; P = .014) and similar severe cardiac (13.8% vs 10%; P = .69) complications compared with diabetics not taking metformin.

Discussion: Diabetic patients with NSCLC or EC taking metformin who were treated with concurrent chemoradiation therapy experienced similar pulmonary, esophageal, and cardiac toxicities compared with patients using alternate methods of glycemic control. Importantly, these data suggest that metformin may be safely used concurrently with chemoradiation treatment. This is encouraging, given that metformin is a radiosensitizer agent associated with improved rates of pathologic complete response. Indeed, a national trial is currently being considered that would incorporate metformin into standard multimodality treatment for NSCLC. These data provide preliminary evidence to support the safety of such a trial.

References:

1. Skinner HD, McCurdy MR, Echeverria AE, et al. Metformin use and improved response to therapy in esophageal adenocarcinoma. Acta Oncol. 2013;52:1002-9.

2. Fakhreddine M, Liao Z, Zhuang Y, et al. Poor glycemic control during radiochemotherapy contributes to reduced local control and overall survival in patients with non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2012;84:S69-70.