reports

Metformin use is associated with lower cervical cancer specific mortality

Radiation Oncology 93:S10.

University of Toronto, Toronto, ON, Canada; Women’s College Hospital, Toronto, ON, Canada

Purpose/Objective(s): While meta-analysis has shown metformin use in diabetic patients to be associated with lower cancer risk and mortality, none of the previous studies focused on cervical cancer. The purpose of this study was to examine the association between metformin use and mortality in patients with cervical cancer.

Materials/Methods: Using Ontario health databases, a retrospective, population-based cohort study was conducted on women with diabetes over the age of 65 years diagnosed with cervical cancer between 1997 and 2010. Those who did not receive definitive treatment (surgery, radical radiation therapy, or chemoradiation) were excluded. The primary objective was to examine the effect of metformin exposure after cervical cancer diagnosis on cervical cancer-specific mortality. Regression analysis was performed using the Fine and Gray model, with non-cancer death as a competing risk and metformin use as a time-varying exposure. A clinical model was first built using backwards elimination, considering the following covariates: year of diagnosis, socioeconomic status, age, histology, treatment, diabetes duration, and the Johns Hopkins comorbidity index (aggregated diagnosis groups). Time-varying medication exposures (metformin, other oral hypoglycemic drugs, and insulin) were then added to the clinical model to test their independent association with cervical cancer-specific mortality.

Results: The cohort consisted of 181 diabetic patients with cervical cancer, with a median follow-up of 5.8 years (interquartile rangeZ4.2e9.7 years) for alive patients. There were 61 cervical cancer-specific deaths (34%) and 68 non-cancer deaths (38%). Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a significant decreased risk of cervical cancer-specific mortality in a dose-dependent fashion (HR Z 0.72 for each additional 500 g of metformin use, 95% CI Z 0.53e0.98, P Z .03). Sensitivity analysis also found a significant association between cumulative dose of metformin and cervical cancer-specific mortality when the cohort was limited to the 124 women who were treated with definitive (chemo)radiation (HR Z 0.69 for each additional 500 g of metformin use, 95% CI Z0.49e0.96, PZ .03). There was no association between cumulative use of other antidiabetic drugs and cervical cancer-specific mortality.

Conclusion: To our knowledge, this is the first clinical study on metformin in cervical cancer, and it showed a cumulative dose of metformin to be independently associated with lower cervical cancer-specific mortality.