Amifostine Trial Represents First FDA Approval of Treatment Interacting With Radiation

August 2, 2001

DURHAM, North Carolina-"We have a positive randomized trial of amifostine (Ethyol), and it represents the first time that a treatment has been approved by the Food and Drug Administration (FDA) that interacts with radiation therapy," David M. Brizel, MD, said.

DURHAM, North Carolina—"We have a positive randomized trial of amifostine (Ethyol), and it represents the first time that a treatment has been approved by the Food and Drug Administration (FDA) that interacts with radiation therapy," David M. Brizel, MD, said.

An associate professor in the Department of Radiation Oncology at Duke University Medical Center in Durham, North Carolina, Dr. Brizel reviewed radioprotection concerns. "First, it is fairly obvious that we are aiming to reduce the toxicity of our anticancer treatment. With amifostine the endpoints relating to this consideration have been xerostomia and mucositis," he said. "The second consideration is that when we start to perturb the system, we must be certain that we not compromise the effectiveness of anticancer treatment. Also, we have to be certain that we are not simply trading one toxicity for another."

Proof of Principle

The positive trial Dr. Brizel referred to is the WR-38 study showing that patients pretreated with amifostine had significantly better unstimulated saliva production 1 year after radiotherapy. The WR-38 trial was the first proof of principle that a chemical radioprotection strategy could be incorporated into radiotherapy for head and neck cancer in a prospective, randomized trial.

"We still don’t know what is the optimal schedule or the optimal dosage for amifostine," Dr. Brizel acknowledged.

Keratinocyte Growth Factor

Another new drug in development is keratinocyte growth factor (KGF), a member of the fibroblast growth factor family. It is a glycoprotein, and a very potent stimulant for the proliferation of normal epithelial cells. KGF stimulates the proliferation of type-2 pneumocytes and also helps differentiate them back toward type-1 pneumocytes, the cells in the alveoli responsible for oxygen exchange.

A phase II trial of KGF has been completed among advanced head and neck cancer patients receiving either hyperfractionated irradiation and concurrent platinum-fluorouracil or once daily fractionation. One dose of KGF was given prior to the start of chemotherapy and radiation. KGF was also given at the end of each week of treatment, with two additional administrations of the drug in each of the weeks following completion of chemoradiotherapy.

"I think we should look prospectively at physical strategies and pharmacologic strategies, either in head-to-head comparisons or as complementary treatments, and continue the search for more effective, less toxic ways of delivering these drugs," Dr. Brizel said.