SAN ANTONIO – Metformin use during radiotherapy for endometrial cancer was associated with significantly better disease-free survival (DFS) in a retrospective study presented at the annual of the American Society for Radiation Oncology.

Dr. Jim Zhong of Emory University, Atlanta, who reported the findings also said that there was a “positive trend” in local control and in metastasis-free survival (MFS). “These hypothesis-generating data warrant further study,” he said.

The study included 185 women who had been diagnosed and treated with definitive surgery and adjuvant radiotherapy at Emory University Hospitals between 1999 and 2013. The median age of women was 61.5 years, and 32 were treated with metformin vs. 153 who were not. The majority of women in both study arms had early-stage (IA) disease (50% in the metformin arm and 41% in the no metformin arm; P = .44).

After a median follow-up of 49 months, all disease-related endpoints favored the use of metformin, Dr. Zhong said. DFS was 80.3% in the metformin-treated women and 59.5% in the women who did not receive this oral antidiabetic drug (P =.03). The hazard ratio was 0.32 with a 95% confidence interval of 0.12-0.89.

Local control was 83.5% vs. 69.9% (HR, 0.37; 95% CI 0.11-1.19; P = .08), MFS was 96.2% vs. 85.2% (P = .13) and overall survival was 83.2% vs. 79.1% (HR, 1.02; 95% CI 0.42-2.46; P = .09).

In another retrospective study, reported by Dr. Kathy Han of the Princess Margaret Cancer Center at the University of Toronto, the cumulative dose of metformin was independently associated with reduced cancer-specific mortality in women who had received definitive treatment for cervical cancer that had included radiotherapy.

“There has been a lot of interest in repurposing metformin as an anticancer agent because retrospective epidemiological studies have shown that diabetic patients who took metformin had lower cancer incidence and mortality, compared to those that did not take metformin ” Dr. Han explained. None of the previous studies had looked at cervical cancer, she added.

Data from several Ontario and Canadian health databases were used to conduct a population-based cohort study involving 181 women aged 65 years or older who had diabetes and had been diagnosed with and received definitive treatment for cervical cancer between 1997 and 2010. At a median follow-up was 5.8 years, there were 61 (34%) cervical cancer-specific and 68 (38%) noncancer deaths.

Dr. Han reported that for each additional 365g of metformin used, the hazard ratio for cervical cancer-specific death was 0.79 (95% CI 0.63-0.98; P = .03). There was no such association for other antidiabetic drugs used.

“To explore this further we recently activated a phase II randomized study of standard chemoradiation with or without metformin in nondiabetic women with locally advanced cervical cancer,” Dr. Han said. “In this study we are only including women with hypoxic tumors,” she noted, the reason being that hypoxic tumors are known to be resistant to radiation so if metformin does have an effect there should be a better response to radiation therapy.

In a separate presentation, Dr. Jeffrey Gross of Northwestern University in Chicago reported the results of a retrospective case review study that investigated the impact of hyperglycemia on outcomes in 84 women with stage IB1 to IVB cervical cancer who had definitive chemoradiation at his institution over a 9-year period starting in 2000. The median age of women was 48 years. Four women had type 2 diabetes mellitus and three were taking antidiabetic medications (two metformin and one insulin). The median follow up was 38.5 months.

Posttreatment hyperglycemia, defined as an average of random blood glucose measurements of 110 g/dL or higher, was found to be associated with poorer locoregional control at 5 years. Locoregional control rates were 67.1% in women who had high posttreatment blood glucose levels compared 90.6% in women with normal glycemic status (P = .02).

There was also a nonsignificant trend toward worse OS at 5 years in the women who had hyperglycemia following chemoradiation vs. those who did not (76.8% vs. 55.7%; P = .08).

There was no observable correlation between the high level of blood glucose and standard prognostic factors such as stage or nodal positivity, Dr. Gross said.

“The suggestion that hyperglycemia after chemoradiation for cervical cancer confers a poor prognosis is a novel finding,” Dr. Gross and coauthors concluded in their abstract. “Further investigation is needed to characterize the relationship between hyperglycemia, tumor genomics, and treatment outcomes,” they added.

Commenting on the potential for metformin and countering hyperglycemia to improve the outcomes of (chemo)radiation in these gynecologic tumors, Dr. Larissa Lee of Brigham and Women’s Hospital in Boston who comoderated the session at which the studies were presented said: “It is very much an exciting area for clinical research, but we do need to do a lot more steps in terms of validation.”

Metformin could have an effect on radiation response, she noted, but “it is something we have only been seeing in the retrospective studies presented today, but it would be interesting to look at this in a prospective study.”

ASTRO: Metformin use during radiotherapy associated with better gynecologic cancer outcomes