Metformin use after Cervical Cancer Diagnosis among Older Women with Diabetes may be Associated with a Significant Decrease in Mortality
1Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
2Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
3Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
4Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada.
5Institute of Clinical Evaluative Studies, Toronto, Ontario, Canada.
Kathy Han, Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. Phone: 141-6946-2919; Fax: 141-6946-6561; E-mail: Kathy.Han@rmp.uhn.on.ca
Note: M.F. Milosevic and A.W. Fyles contributed equally to this article.
Background: To examine the association between metformin use and mortality in patients with diabetes and cervical cancer.
Methods: Using Ontario health databases, a retrospective, population-based cohort study was conducted in women with diabetes ≥ age 66 years diagnosed with cervical cancer between 1997 and 2010. The association between metformin exposure and cervical cancer–specific mortality was examined using Fine–Gray regression models, with noncancer death as a competing risk and cumulative metformin use as a time-varying exposure. The association with overall mortality was examined using Cox regression models.
Results: Among the 181 women with diabetes and cervical cancer, there were 129 deaths, including 61 cervical cancer–specific deaths. The median follow-up was 5.8 years (interquartile range 4.2–9.6 years) for surviving patients. Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer–specific mortality and overall mortality in a dose-dependent fashion [HR 0.79; 95% confidence interval (CI), 0.63–0.98; and HR 0.95; 95% CI, 0.90–0.996 per each additional 365 g of metformin use, respectively]. There was no significant association between cumulative use of other antidiabetic drugs and cervical cancer–specific mortality.
Conclusion: This study suggests an association between cumulative metformin use after cervical cancer diagnosis and lower cervical cancer–specific and overall mortality among older women with diabetes.
Impact: Cumulative dose of metformin use after cervical cancer diagnosis among older women with diabetes may be associated with a significant decrease in mortality. This finding has important implications if validated prospectively, as metformin is inexpensive and can be easily combined with standard treatment for cervical cancer. Cancer Epidemiol Biomarkers Prev; 25(3); 507–12. ©2015 AACR.
Received September 29, 2015.
Revision received December 18, 2015.
Accepted December 18, 2015.
©2015 American Association for Cancer Research.