Amifostine reduces radiochemotherapy-induced toxicities in patients with locally advanced non-small cell lung cancer

Abstract

Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small cell lung cancer, but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), a radioprotector, could reduce the incidence of RCT-induced acute and late toxicities. Between October 1997 and August 1999, 73 patients with previously untreated stage IIIa–IIIb non-small cell lung cancer were randomized to treatment with RCT alone or RCT plus amifostine (300 mg/m 2 daily intravenous infusion). Chemotherapy consisted of either paclitaxel (60 mg/m 2) or carboplatin (area under the concentration-curve of 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy daily fraction, 5 days a week to a total dose of 55 to 60 Gy. Esophagitis and acute lung toxicity were evaluated during treatment; late lung toxicity was assessed at 3 and 6 months after RCT and was graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria. Esophageal endoscopy was performed the fourth week during RCT and 1 month after the end of RCT. Endoscopic findings of radiation esophagitis were scored from 0 to 3. There was no significant difference between treatment arms in baseline patient characteristics. A total of 68 patients were evaluable for toxicity and efficacy (RCT group, n = 32; RCT plus amifostine, n = 36). The incidence of grade ≥ 3 esophagitis during RCT was significantly lower for patients receiving amifostine than for those receiving RCT alone (38.9% v 84.4%; P < .001). The incidence of grade ≥ 3 acute pulmonary toxicity was also significantly reduced in amifostine-treated patients (19.4% v 56.3%; P = .002). At 3 months following RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than those who received RCT alone ( P = .009). Endoscopic grade ≥ 2 esophagitis was observed in eight of 15 patients in the RCT group and in three of 18 patients in the RCT plus amifostine group ( P = .061). No significant differences in response rates were noted between patients receiving RCT with or without amifostine ( P = .498). Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced non-small cell lung cancer without compromising antitumor efficacy.