Diabetes drug metformin with chemo and radiation may improve outcomes in lung cancer patients

Treating aggressive lung cancer with the diabetes drug metformin along with radiation and chemotherapy may slow tumor growth and recurrence, suggests new preliminary findings from researchers at the Perelman School of Medicine at the University of Pennsylvania being presented during an oral abstract session October 28 at the 15th World Conference on Lung Cancer.

The preclinical and clinical results, which have set the stage for a first-of-its-kind prospective study, point to metformin as an effective radiosensitizer - a drug that makes tumor cells more sensitive to radiation therapy - to treat stage III non-small cell lung cancer (NSCLC). Because of poor local response and five-year survival rates around 15 percent in late-stage NSCLC patients, well-tolerated, combination therapies are greatly needed.

The abstract is being presented by Ildiko Csiki, MD, PhD, an assistant professor of Radiation Oncology at Penn's Abramson Cancer Center.

Metformin, the most-widely used drug for type-2 diabetes, has been shown to have anti-cancer effects on a number of cancers, including prostate and colon. It activates AMP-related pathways, leading to inactivation of mTOR and suppression of its downstream effectors, a crucial signaling pathway for proliferation and survival of cancer. However, little data exists to support its role in NSCLC. And its role as a radiosensitizer in lung cancer is even less understood.

For this study, clinical evidence from 16 diabetic patients treated at the Hospital of the University of Pennsylvania between June 2008 and June 2013 with stage III A and B NSCLC and diabetes demonstrated that chemoradiation therapy in combination with metformin dramatically improved local recurrence. With a median follow-up time of 10.4 months, only two local recurrences have occurred.

Researchers also observed a survival benefit with the combination.

Ever since discovering a decade ago that a gene altered in lung cancer regulated an enzyme used in therapies against diabetes, Reuben Shaw has wondered if drugs originally designed to treat metabolic diseases could also work against cancer.

The growing evidence that cancer and metabolism are connected, emerging from a number of laboratories around the world over the past 10 years, has further fueled these hopes, though scientists are still working to identify what tumors might be most responsive and which drugs most useful.

Now, in a new study in the journal Cancer Cell, Shaw and a team of scientists at the Salk Institute for Biological Studies found that phenformin, a derivative of the widely-used diabetes drug metformin, decreased the size of lung tumors in mice and increased the animals' survival. The findings may give hope to the nearly 30 percent of patients with non-small cell lung cancer (NSCLC) whose tumors lack LKB1 (also called STK11).