Amifostine May Prevent Esophagitis in Lung Cancer Patients

NEW YORK—Esophagitis was less frequent and less severe in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with standard chemotherapy and thoracic radiation when amifostine (Ethyol) was added to the regimen, according to a report at the Chemotherapy Foundation Symposium XVII.

Maria Werner-Wasik, MD, assistant professor of radiation oncology, Bodine Center for Cancer Treatment, Thomas Jefferson University Hospital, Philadelphia, reported that in 11 sequential patients given amifostine, 2 patients had no esophagitis, 6 had grade 1 esophagitis, 2 grade 2, and only 1 grade 3. In contrast, in the sequential cohort not receiving the agent, all patients had esophagitis—4 grade 1, 5 grade 2, and 2 grade 3.

Although the study was not randomized, the patient characteristics of the two groups were similar, Dr. Werner-Wasik said. She noted that both groups were poor-prognosis patients. Weight loss at presentation ranged up to 19%, with an average of 5.1% in the patients receiving amifostine and 5.6% in the comparative group.

The chemoradiation therapy given all patients included induction paclitaxel (Taxol) at 225 mg/m² and carboplatin (Paraplatin) dosed to AUC 6 for two cycles, followed by concurrent thoracic radiation at 62.4 Gy and 60 mg/m² paclitaxel weekly. This protocol has been used at the hospital since 1995 for patients with NSCLC with unfavorable prognostic features such as weight loss or mild anemia. In the study, amifostine was given twice weekly—before radiation therapy—in an intravenous dose of 500 mg.

Amifostine was well tolerated, Dr. Werner-Wasik reported. “One patient had an allergic skin rash, and amifostine had to be stopped after five doses,” she said. “One patient had transient hypertension.”

An esophagitis index developed for the study plotted duration and maximum toxicity. Although the median values were similar in the two patient groups, extremely high esophagitis values were more frequent in patients not receiving amifostine than in those given the agent, she said.

Median survival for patients receiving amifostine was 14.5 months and 11 months for the others. “Addition of amifostine did not result in compromised patient survival,” she said.

Greek Study Results

Dr. Werner-Wasik also cited results of a larger study, reported at the 41st annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), held in San Antonio.

In this multicenter Greek study, more than 140 patients with advanced-stage lung cancer were randomized to receive either standard radiation therapy alone or standard radiation therapy with daily pretreatment with amifostine (340 mg/m²) before each radiation fraction. “There was no chemotherapy used in this study,” she said.

The Greek researchers found a significant reduction in radiation-induced pneumonitis 2 months after the end of treatment (P < .001) in the amifostine arm, as well as a significantly reduced incidence of grade 2 or higher esophagitis during the last weeks of treatment. Amifostine administration was well tolerated, and antitumor efficacy was not compromised with use of amifostine.

Mechanism of Action

The mechanism of action of amifostine is believed to be its selective uptake in normal tissue. “Amifostine floods, so to speak, normal tissue in the kidney, lung, liver, marrow, spleen, and other organs,” Dr. Werner-Wasik explained, “whereas the amifostine concentration over time rises very slowly in the tumor, accounting for the differential possibilities for cytoprotection.”

Dr. Werner-Wasik and her colleagues are now engaged in a dose-escalation study in which amifostine is given three times a week.