Antonadou Dosia, Petridis Aris, Synodinou Maria, Throuvalas Nicolas, Bolanos Nicolas, Veslemes Marinos, Sagriotis Alexandros
Radiation Oncology Department, Metaxas Cancer Hospital, Piraeus, Greece.
Semin Oncol. 2003 Dec;30(6 Suppl 18):2-9. doi: 10.1053/j.seminoncol.2003.11.008.
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.
放化疗（RCT）是局部晚期非小细胞肺癌的一种有效治疗方法，但可能会受到急性和晚期毒性（食管炎、肺炎和骨髓抑制）的限制。本试验研究了使用放射防护剂氨磷汀（Ethyol，WR - 2721；MedImmune公司，马里兰州盖瑟斯堡）进行预处理是否能降低RCT诱导的急性和晚期毒性的发生率。在1997年10月至1999年8月期间，73例先前未接受治疗的IIIa - IIIb期非小细胞肺癌患者被随机分为单独接受RCT治疗或RCT联合氨磷汀（每日300 mg/m²静脉输注）治疗。化疗方案为在为期5至6周的常规放疗过程中，每周一次使用紫杉醇（60 mg/m²）或卡铂（浓度 - 曲线下面积为2），常规放疗为每日2 Gy，每周5天，总剂量为55至60 Gy。在治疗期间评估食管炎和急性肺毒性；在RCT后3个月和6个月评估晚期肺毒性，并根据放射肿瘤学组/欧洲癌症研究与治疗组织的标准从0至4级进行分级。在RCT的第四周以及RCT结束后1个月进行食管内镜检查。放射食管炎的内镜检查结果从0至3分进行评分。各治疗组患者的基线特征无显著差异。共有68例患者可评估毒性和疗效（RCT组，n = 32；RCT联合氨磷汀组，n = 36）。接受氨磷汀治疗的患者在RCT期间≥3级食管炎的发生率显著低于单独接受RCT治疗的患者（38.9%对84.4%；P <.001）。氨磷汀治疗的患者≥3级急性肺毒性的发生率也显著降低（19.4%对56.3%；P =.002）。在RCT后3个月，接受氨磷汀治疗的患者肺炎发生率显著低于单独接受RCT治疗的患者（P =.009）。RCT组15例患者中有8例观察到内镜下≥2级食管炎，RCT联合氨磷汀组18例患者中有3例（P =.061）。接受或未接受氨磷汀的RCT患者之间的缓解率无显著差异（P =.498）。氨磷汀可有效降低局部晚期非小细胞肺癌患者RCT相关的急性和晚期毒性的发生率，且不影响抗肿瘤疗效。
