Abstract LB-17: Missing the benefit of metformin in AML: A problem of contrast.
Authors: Wintrob Zachary A. P. , Chuang Huan-Ching , Miller Dustyn S. , Rabey Jonathan L. , Bui Thang Q. , Amsler Michelle E. , Ford Laurie-Ann , Wetzler Meir , Ceacareanu Alice C. 
Published: August 2014

Background: Association of non-secretagogues, metformin and thiazolidindiones, with lower cancer risk and improved survival has led to numerous clinical studies exploring their benefit as adjuvants in cancer chemotherapy. However, the most utilized, metformin, is contraindicated in patients undergoing radiologic studies involving intravenous administration of iodinated contrast media, such as patients with acute myeloid leukemia (AML). In these patients, metformin should be either withheld until renal function returns to normal or substituted with an alternate, in practice, often injectable insulin. Little is known about the consequences of metformin's substitution in patients whose cancer care requires periodic exposures to contrast dye or in which its reinitiation appears unsafe.

Objective: This study compares the utilization of insulin and non-secretagogues, metformin and thiazolidindiones, in patients with diabetes mellitus newly diagnosed with AML or solid tumors.

Methods: All diabetes mellitus (DM) patients diagnosed with AML (n1=65), breast (n2=290), ovarian (n3=46), prostate (n4=105) and kidney cancer (n5=95) between January 2003 and December 2010 at Roswell Park Cancer Institute in Buffalo, NY were included in the study (n=601). Patient demographics, tumor pathology, outcomes, baseline co-morbidities and self-reported drug therapy were documented. Follow-up began at cancer diagnosis and ended with first confirmed recurrence and/or death. Cases lost to follow-up were censored at the date of last contact. Kaplan-Meyer with log-rank statistics and Cox proportional hazards models were used for all multivariate analyses. A nominal significance level of 0.05 was used in all testing.

Results: The median age was 62 years old in the solid tumor group and 69.5 years old in the AML group. Baseline utilization of non-secretagogues in DM patients diagnosed with solid tumors was associated with significantly improved overall mortality, as compared to baseline insulin utilization (X2=4.071, P=0.044). No baseline glucose lowering drug class utilization advantage was observed in the AML group. A stratified analysis of solid tumors and AML groups according to the respective drug utilization revealed a statistically significant difference in mortality in the favor of non-secretagogue utilization in DM patients with solid tumors, but not with AML (X2=258.36, p&lt;0.001).

Conclusion: We confirm a survival benefit for the patients receiving non-secretagogues as compared to insulin in the solid tumors group. The absence of non-secretagogue protection in the AML group could be potentially attributed to the substitution of metformin with injectable insulin at the time of AML diagnosis.

Citation Format: Zachary A. P. Wintrob, Huan-Ching Chuang, Dustyn S. Miller, Jonathan L. Rabey, Thang Q. Bui, Michelle E. Amsler, Laurie-Ann Ford, Meir Wetzler, Alice C. Ceacareanu. Missing the benefit of metformin in AML: A problem of contrast. [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 LB-17. doi:10.1158/1538-7445.AM2013-LB-17