A small study has indicated that patients with advanced non-small cell lung cancer can safely take an experimental oral drug intended to protect healthy tissue from the effects of radiation, according to researchers at the University of Pittsburgh Cancer Institute (UPCI). The study, published in this month's Human Gene Therapy, supports further clinical testing of manganese superoxide dismutase.
A common toxicity of lung cancer radiation therapy is esophagitis. Within a few weeks of treatment, patients typically experience painful swallowing that over time can become so severe that narcotics or a break from radiotherapy may be necessary for patient comfort.
For the safety study, 10 patients with inoperable stage III non-small cell lung cancer took oral doses of manganese superoxide dismutase (MnSOD) plasmid liposome twice-weekly for a total of 14 doses during seven weeks of conventional chemotherapy and radiation treatment. The agent, which boosts levels of an antioxidant the body makes naturally, is made of fat droplets containing the gene that produces MnSOD. When swallowed, it is absorbed by cells in the esophagus.
"The results of this initial trial indicate that MnSOD plasmid liposome can be safely administered," offered senior investigator Joel S. Greenberger, MD, professor and chair in the department of radiation oncology, University of Pittsburgh School of Medicine, and co-director of the lung and esophageal cancer program at UPCI.
"It did not linger in normal cells after treatment, nor did it protect cancer cells from radiation treatment. The next study, which is underway at UPCI, is to determine whether it protects normal tissue, particularly the esophagus, from radiation exposure."
Preclinical testing has shown that generating higher levels of MnSOD in healthy cells can suppress the production of inflammatory molecules and reduce cell death, micro-ulceration and esophagitis. Because the agent is delivered to healthy tissue, it does not protect tumor cells from radiation treatment. In fact, Greenberger noted, experiments hint that when it is given to cancer cells, it actually encourages cell death because of abnormalities in their cellular metabolism.
"If we can sufficiently protect tissues that are normal, we should be able to deliver our cancer treatments more effectively and perhaps even at higher doses," Greenberger added.