Metformin Use and Improved Response to Therapy in Esophageal Adenocarcinoma

Background: We investigated the radiographic and pathologic response rate of esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients taking metformin.

Material And Methods: Two hundred eighty-five patients with esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed by esophagectomy from 1997 to 2012 were included in the study, including 29 diabetics taking metformin, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post-treatment positron emission tomography (PET) scans were available for 204 patients. Pathologic response was graded at the time of surgery. Response rates were compared using both the χ(2) statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT.

Results: The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with ≥ 1500 mg/d associated with a higher CR rate. No significant difference seen in pre-CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly decreased in patients taking metformin (p = 0.05). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in field loco-regional failure following radiation (p = 0.05).

Conclusion: Metformin use is associated with a dose-dependent increased response to CRT in esophageal cancer and may be a sensitizer to this therapy.