HOUSTON—Amifostine (Ethyol) can reduce the risk of acute pneumonitis and severe esophagitis associated with concurrent radiation and chemotherapy administered to patients with advanced non-small-cell lung cancer (NSCLC). Results of a phase III study were reported by Ritsuko Komaki, MD, professor of radiation oncology at the University of Texas M.D. Anderson Cancer Center in Houston.
"The purpose of this trial was to compare esophageal toxicity of grade 3 to 4, including severe dysphagia and odynophagia, in patients who received chemoradiotherapy with or without amifostine(Drug information on amifostine). The trial also compared hematologic and pulmonary toxicity. Secondary endpoints were survival, local control and distant metastasis," Dr. Komaki said. Toxicities were scored using Radiation Therapy Oncology Group (RTOG) criteria. The study was designed with the power to detect a 50% reduction in the rate of severe acute esophagitis.
Amifostine was chosen for this study because it has protective abilities against nephrotoxicity, hematologic toxicity, neurologic toxicity, and radiation-induced injury, Dr. Komaki explained.
Eligibility criteria included medically inoperable stage II and stage IIIA or IIIB NSCLC, no major weight loss, and no pleural effusion, prior chemotherapy, or prior radiation therapy. "We had only two patients with medically inoperable stage II disease. The majority of the patients were surgically inoperable stage IIIB," Dr. Komaki said.
Randomized to Two Arms
Twenty-seven patients were randomized to arm I (chemoradiation with amifostine) and 26 were randomized to arm II (chemoradiation without amifostine). Patients in arm I received amifostine, 500 mg IV over 5 minutes, 15 minutes before cisplatin(Drug information on cisplatin) (Platinol) infusion on days 1, 8, 29, and 36, and 500 mg IV over 5 minutes, 30-60 minutes before the first daily fraction of radiation on days 2, 9, 15, 16, 22, 23, 30, and 37.
"The regimen was slightly different from that in RTOG 98-01. We used oral etoposide(Drug information on etoposide) and cisplatin and radiation therapy in 1.2 Gy twice-daily fractionations, with a 6-hour interfractional interval, and the total tumor dose of 69.6 Gy. There was no induction chemotherapy," Dr. Komaki said. "We gave the amifostine at 7 o’clock in the morning."
