Combining Metformin With Chemotherapy 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, suggested new preliminary findings from researchers at the Perelman School of Medicine at the University of Pennsylvania. The findings will be presented by Ildiko Csiki, MD, PhD, during an oral abstract session at 15th World Conference on Lung Cancer, to be held October 27 to October 30 in Sydney (Abstract MO05.10).
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 to treat stage III non–small cell lung cancer (NSCLC). Because of poor local response and 5-year survival rates of around 15% in patients with late-stage NSCLC, well-tolerated combination therapies are greatly needed.
Metformin, the most widely used drug for type 2 diabetes, has been shown to have anticancer effects on a number of cancers, including those of the 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, few data exist to support its role in NSCLC, and its role as a radiosensitizer in lung cancer is even less understood.
Addition of Metformin Improves Local Recurrence
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 IIIA and IIIB 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.
“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 Dr. Csiki, who is Assistant Professor of Radiation Oncology at the Abramson Cancer Center.
Potential Use as a Radiosensitizing Agent
Researchers developed a mouse model of lung cancer to evaluate the tumor growth delay after using metformin as a radiosensitizing agent. They tracked tumor size in mice injected with metformin undergoing radiation and chemotherapy. Tumor measurements were taken every other day, and tumor growth delay was plotted.
Early data from those experiments support the use of metformin as a radiosensitizing agent, said Dr. 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.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
