Metformin May Improve Remission Rates in Thyroid Cancer

Metformin molecule isolated on whitePatients with both type 2 diabetes and thyroid cancer are more likely to achieve complete remission if they take metformin than if they do not, according to findings from a retrospective study published in the Journal of Clinical Endocrinology and Metabolism. Metformin also inhibited growth of thyroid cancer cell in vitro.

"We believe that this anti-diabetic drug with a well established safety profile could be quickly repositioned for the treatment of patients with thyroid cancer," said senior author Vasyl Vasko MD, PhD, research scientist, Uniformed Services University of the Health Sciences, Bethesda, MD. "However, clinical trials with metformin need to be performed to confirm these findings," he noted.

"Retrospective research should be best regarded as hypothesis-generating rather than definitive," commented Javier A. Menéndez, PhD, Head of the Translational Research Laboratory at the Catalan Institute of Oncology in Girona, Catalonia, Spain. "Nevertheless, the new study by Vasko and colleagues clearly supports the justification for further translational research approaches guiding a better design of metformin-based clinical trials," Dr. Menéndez said.

"Frustrated by the gene-centric limitations of conventional approaches to cancer treatment, perhaps it is time to definitely adopt the view that cancer diseases are governed also by a pivotal regulatory role of metabolic reprogramming," Dr. Menéndez added.

Retrospective Study Design
The authors performed a retrospective analysis of medical records from patients with thyroid cancer and type 2 diabetes who were treated with (n=34) or without (n=21) metformin. A matched control group of patients with thyroid cancer but not diabetes also was evaluated. All patients were followed for approximately 7 years.

Patients with both diseases who used metformin had a smaller tumor size at the time of surgery than those who did not use metformin or were in the control group (1.37 cm vs 2.44 cm and vs 2.39 cm; P=0.026).

More than 80% of Patients Taking Metformin Achieved Remission
While 82.4% of patients with comorbid disease who took metformin achieved complete remission, the rate was significantly lower in patients who did not take metformin (57.1%; P=0.029) and was similar to that in the control group (81.6%). The link between metformin and complete remission increased with higher doses (P=0.05) but was not associated with duration of use.

A decreased likelihood of achieving a complete response was significantly associated with nonuse of metformin in patients with comorbid disease (odds ratio [OR], 0.03), gross extrathyroid extension (OR, 0.09) and distant metastases (OR, 0.005; P<0.001 for all comparisons), according to a multivariate analysis. In addition, the following factors were significantly associated with a shorter progression free survival in a Cox proportional hazards model: age (hazard ratio [HR], 1.059), presence of lymph node metastases (HR, 7.614), lack of metformin treatment (HR, 9.218), and presence of distant metastases (HR, 17.359).

In Vitro Findings Support Use of Metformin
An in vitro study using thyroid cancer cell lines showed that metformin inhibited cancer cell growth and that p70S6K/pS6 signaling appears to be a molecular target of metformin in thyroid cancer cells.

"Our in vitro experiments allow us to identify molecular markers that can be used for the prediction of the cancer cell response to the treatment with metformin," Dr. Vasko said. "We believe that identification of these markers in patients with thyroid cancer can guide clinicians in determining individualized use of metformin. We believe that personalized approach, based on specific genetic and molecular signature of cancer in a given patient can represent a basis for the selection of optimal therapeutic strategy," he concluded.

"The study by Vasko et al and other ongoing clinico-molecular studies on the anticancer activity of the biguanide metformin should provide the basis to accelerate and diversify our current therapeutic capacity in new clinical trials designed to target commonly observed tumors' metabolic addictions," Dr. Menéndez commented.

Klubo-Gwiezdzinska J, Costello J Jr, Patel A, et al. Treatment with metformin is associated with higher remission rate in diabetic patients with thyroid cancer. J Clin Endocrinol Metab. 2013;98(8):3269-3279.

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