Drug shows early promise in protecting lungs from radiation damage

October 22, 2000

Results from a study using rats demonstrate that a currently used drug could also be used to protect lung tissue from damage from radiation therapy aimed at tumors in or near the lungs, Duke University researchers report.

Lung injury from radiation frequently limits how much radiation can be given, said principal investigator Dr. Mitchell Anscher, professor of radiation oncology at Duke. Protecting normal tissue would allow more radiation to be given to the tumor, improving the chances for effective radiotherapy, he added.

The drug, called amifostine, is used in humans to protect normal tissue from damage due to chemotherapy. But in their study with rats, the researchers showed it also effectively reduces radiation damage in the normal lungs without protecting the tumor.

"Fibrosis, or scar tissue, is a consequence of radiation-induced lung injury that disables patients and reduces their quality of life," said lead author Dr. Zeljko Vujaskovic, assistant professor of radiation oncology at Duke Comprehensive Cancer Center. "With amifostine, the possibility exists that we could reduce the incidence of fibrosis."

The scientists also found that blood levels of a protein, called TGF-beta, or transforming growth factor beta, can be used to evaluate lung damage and its moderation with drugs like amifostine. "We wondered if we could moderate injury by using amifostine, would that reduction be reflected in plasma levels of TGF-beta?" Vujaskovic said. "Our study showed a strong association that if amifostine reduced lung injury, that levels of TGF-beta were also reduced."

Results of the study were prepared for presentation Monday at the annual meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO). A separate Duke study being presented at ASTRO demonstrates that TGF-beta can be used to predict risk of radiation-induced lung damage in patients.

Radiation kills cells indirectly, by creating highly reactive oxygen atoms, called free radicals, that can cause enough cumulative damage to DNA that the cell begins to die. Some chemotherapy drugs work by creating free radicals, too.

Amifostine is one potential agent for protecting normal tissue from the free radicals caused by radiation treatment by decreasing the chances that a cell's DNA will be damaged.

While chemotherapy and radiation are supposed to kill cancer cells, inevitably some normal cells are hurt as well. Radiation damage can be minimized through sophisticated techniques such as three-dimensional conformal radiotherapy which, by determining the location, size and relationship to nearby critical organs in three dimensions, allows radiation to be pinpointed to the tumor. But even though damage is minimized, it still happens, said the researchers.

Beyond improving quality of life, preventing lung damage could lead to better treatment and improved survival, the researchers said. Lung, breast and esophageal cancer and lymphoma are just a few of the diseases that can result in radiation treatment that affects the lungs.

"If we could block this damage of normal tissue, we could potentially increase the radiation dose to the tumor without creating intolerable injury to the normal lung," explained Anscher. "Studies have shown that increasing radiation doses in the treatment of lung cancer might be able to increase cure rates."

The scientists, particularly Qinfu Feng, developed an animal model to evaluate amifostine's effects on lung and tumor damage from radiation. In rats, breast cancer cells were implanted near the right lung. Some rats received radiation therapy and amifostine for five days, some radiation only, some amifostine only, and some only anesthesia. Rats without implanted tumors were studied as well.

Feng, a visiting scientist from the Cancer Hospital at the Chinese Academy of Medical Science in Beijing, evaluated each rat for effects of the drug or radiation, particularly weight loss and changes in breathing rates. An increased breathing rate indicated damage to the lungs, much as shortness of breath is common in humans.

The scientists found that amifostine did not affect tumor growth rate, which means that it doesn't protect a tumor, they said. In rats without tumors, amifostine significantly delayed and reduced lung damage from radiation, said the researchers.

"We found in our rat model of radiation-induced lung injury significant increase in lung tolerance to radiation with amifostine," said Feng.

A separate report this month from other Duke researchers showed that amifostine protects against radiation treatment side effects in patients with head and neck cancer. In addition to Vujaskovic, Feng and Anscher, Dr. David Brizel, associate professor of radiation oncology at Duke, was a co-author of the study.
Contact: Joanna Downer

Duke University Medical Center

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