Abstract

Abstract Rationale. In observational and preclinical studies, metformin is found to have anticancer properties and to prolong survival in various cancer types. It is unknown whether metformin use confers a survival benefit in Small Call Lung Cancer (SCLC) patients. We studied the influence of metformin usage on the overall survival (OS) in SCLC patients. Methods. SCLC patients in the period 1998 to 2009 were selected from the population-based Eindhoven Cancer Registry. Those included were linked to the PHARMO Record Linkage System. The following data were recorded: date of diagnosis, age, gender, stage of disease, comorbidity (Charlson comorbidity index), drug usage, administration of chemotherapy and date of death. Kaplan Meier curves were used to estimate OS. Cox regression analyses were used to estimate the hazard ratio (HR), this was corrected for age, gender and stage of disease in multivariate analyses. Due to the small group of patients using metformin, a multivariate analysis to correct the HR estimation was not performed. Results. In this study, a total of 1,136 SCLC patients were included. Median age was 67 years (range 37-95), 63%/37% male/female, 63%/37% extended/limited disease. Patients were treated with chemotherapy (75%), radiotherapy (28%) or surgery (2%). A total of 256 patients (23%) did not receive active anticancer treatment. Most common comorbidities were cardiovascular diseases (35%), COPD (24%), and hypertension (19%). A total of 151 patients (12%) were diagnosed with diabetes mellitus (DM), of which 92 (68%) received antidiabetics at time of diagnosis of SCLC. Fifty patients received metformin. DM was not significantly associated with a worse prognosis, with a median OS of 6.0 vs. 7.5 months in patients without DM (HR= 1.2 (95% CI 0.9-1.5)). Patients receiving metformin had no survival benefit comparing to all other SCLC patients, with a median OS of 8.4 and 7.0, respectively (HR= 0.9 (95% CI. 0.7-1.2)). Compared to patients receiving insulin monotherapy or sulfanylureas (n= 42), outcome was non-significantly improved in patients receiving metformin monotherapy (n= 20): median OS 11.0 vs. 7.0 months (HR= 0.9 (95% CI. 0.5-1.6)). Conclusions. In our series, having diabetes was not associated with worse prognosis in SCLC patients. However, within the SCLC patients with diabetes, those receiving metformin had a clinically relevant survival benefit compared to those receiving other antidiabetics. Due to a relative small cohort we could not demonstrate significance. Larger (retro- and) prospective studies and preclinical research must be performed to elucidate the role of metformin, if any, in the clinical management of SCLC. Citation Format: Wouter W. Mellema, Mieke J. Aarts, Myrthe P.P. Van Herk-Sukel, Egbert F. Smit. A retrospective evaluation of metformin usage in patients with small cell lung cancer (SCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3635. doi:10.1158/1538-7445.AM2013-3635

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