Effect of amifostine on toxicities associated with radiochemotherapy 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 (NSCLC), but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine, a radioprotector, could reduce the incidence of radiochemotherapy-induced acute and late toxicities. Between October 1997 and August 1999, 73 patients with previously untreated Stage IIIa-IIIb NSCLC were randomized to treatment with RCT alone (n = 36) or RCT plus amifostine (300 mg/m(2) daily i.v. infusion, n = 37). RCT consisted of either paclitaxel (60 mg/m(2)) or carboplatin (AUC 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy/5 days/week to a total dose of 55 to 60 Gy. Blood cell counts were measured weekly; esophagitis and acute lung toxicity were evaluated during the treatment course. Treatment efficacy was assessed following World Health Organization criteria for response. 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. A total of 68 patients were evaluable for toxicity analysis (RCT group, n = 32; RCT + amifostine, n = 36). There was no significant difference between treatment arms in patient baseline characteristics. The incidence of Grade >or=3 esophagitis during RCT was significantly lower for patients receiving amifostine than for patients receiving RCT alone (38.9% vs. 84.4%%, p < 0.001). Furthermore, the incidence of Grade >or=3 acute pulmonary toxicity was significantly reduced in patients treated with RCT plus amifostine compared to patients who received RCT alone (19.4% vs. 56.3%, p = 0.002). At 3 months after RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than patients who received RCT alone (p = 0.009). Combined response rates (complete plus partial responses) were 82.2% in the RCT group and 88.8% in the RCT plus amifostine group (p = 0.498). Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced NSCLC without compromising antitumor efficacy.