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Metformin Could Serve as a Radiosensitizer to Treat Patients with Stage III NSCLC

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New preliminary findings gathered by researchers from the Perelman School of Medicine at the University of Pennsylvania being presented during an oral abstract session at the 15th World Conference on Lung Cancer, revealed that treating aggressive lung cancer with the diabetes drug metformin, in conjunction with radiation and chemotherapy may slow tumor growth and recurrence.

The pre-clinical and clinical results, which have emgered as the first of their kind setting a precedent, depict 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). Due to poor local response and five-year survival rates around 15 percent in late-stage NSCLC patients, well-tolerated, combination therapies are significantly required.

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

Metformin, which is the most prevalent drug for type-2 diabetes, has been proven to have anti-cancer effects on a variety of cancers, including but not limited to prostate and colon. It engages AMP-related pathways, leading to inactivation of mTOR and suppression of its downstream effectors, a critical signaling pathway for the propagation and survival of cancer.

However, little data exists to support/verify its role in NSCLC. And its role as a radiosensitizer in lung cancer has even less substantial data to be studied and evaluated.

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 showed that chemoradiation therapy in accordance with metformin significantly improved local recurrence. With an average follow-up time of 10.4 months, only two local recurrences have taken place.Metformin Could Serve as a Radiosensitizer to Treat Patients with Stage III NSCL

Researchers also observed a rise in the overall survival rate that accompanied the combination.

"Our clinical experience demonstrates patients receiving definitive chemoradiation for stage III NSCLC who took metformin for diabetes had improved local control and overall survival compared with our patients not taking metformin and compared with historical controls," said Csiki.

On the preclinical spectrum, Penn researchers developed a mouse model of lung cancer in order to assess the tumor growth hindrance after applying metformin as a radiosensitizing agent. They traced tumor size in mice injected with metformin undergoing radiation and chemotherapy. Tumor measurements were recorded every other day and tumor growth delay was schemed.

“Early data from those experiments supports the use of metformin as a radiosensitizing agent,” said Csiki.

"Such findings, along with our clinical retrospective data, will lead to institutional prospective clinical trials, for the first-time, using metformin as a radiosensitizing agent in combination with radiation therapy and chemotherapy in the treatment of lung and potentially other cancers," the authors wrote.

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