Amifostine reduces radiochemotherapy-induced toxicities in patients with locally advanced non-small cell lung cancer.
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 >or= 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 >or= 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 >or= 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.
Antonadou
Dosia
D
Radiation Oncology Department, Metaxas Cancer Hospital, Piraeus, Greece.
Petridis
Aris
A
Synodinou
Maria
M
Throuvalas
Nicolas
N
Bolanos
Nicolas
N
Veslemes
Marinos
M
Sagriotis
Alexandros
A
D000368:Aged; D004999:Amifostine / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects; D004941:Esophagitis / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use; D011832:Radiation Injuries / Q000517:prevention & control*; D017564:Radiation Pneumonitis / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D016190:Carboplatin; D004999:Amifostine; D017239:Paclitaxel