NEW YORKEsophagitis 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 esophagitis4 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
weeklybefore radiation therapyin an intravenous dose of
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,
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,
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