放疗联合化疗及瘤内注射EIB缺失腺病毒(H101)综合治疗鼻咽癌的临床研究

Radiotherapy combined with chemotherapy and intratumoral injection of EIB gene-deleted adenovirus(H101) for nasopharyngeal carcinoma

目的：观察放疗联合化疗及瘤内注射EIB缺失腺病毒（H101）综合治疗鼻咽癌的近期疗效和不良反应。方法：符合入选标准的56例鼻咽癌患者先行化疗和同期颈部肿瘤瘤内注射H101，每天1次，每次1支（5×10^11病毒颗粒数／0．5mL），连续5天，化疗用PF方案（DDP20mg／m^2静滴，d1～d5，5-FU500mg／m^2静滴，d1～d5），21天为1疗程。连续2疗程后进行放疗。结果：56例鼻咽癌患者放疗结束时肿瘤消退率为71．4％，好转率为28．6％。放疗后3个月肿瘤消退率为100％。放疗后6个月有2例颈部肿瘤复发。不良反应为注射部位局部疼痛19．6%，非感染性发热41．7％，流感样症状8．9％，白细胞下降42．9％，恶心呕吐33．9％，口腔黏膜损害100％。结论：放疗联合化疗及基因治疗鼻咽癌有明确的近期疗效，毒副反应轻，可望成为鼻咽癌新的综合治疗模式，远期疗效有待进一步观察。

Objective： To evaluate the short-term effects and toxicities of radiotherapy combined with chemotherapy and intratumoral injection of an EIB gene-deleted adenovirus （H101） in treating patients with nasopharyngeal carcinoma. Methods： A total of 56 patients with nasopharyngeal carcinoma were recruited. They first received chemotherapy based on PF regimen（cisplatin 20 mg/m^2 ivgtt,qd×5 d;5-fluorouracil 500 mg/m^2 ivgtt, qd×5 d）. Cervical intratumoral injection of H101 （5 ×10H viral particle/0.5 mL） was simultaneously administered to patients once daily for 5 consecutive days. Treatment repeated every 3 weeks as 1 cycle. Patients received radiotherapy after they completed 2 cycles of chemotherapy. Results： Among 56 patients, the complete response rate was 71.4% and partial response rate was 28.6% at the end of radiotherapy. The complete response rate was 100% at 3 months after radiotherapy. Recurrence of cervical tumors was found in 2 patients at 6 months after radiotherapy. Main side effects included injection site reaction （19.6 % ）, fever independent of infection（41.7 % ）, flu-like symptom （8.9 % ）, leukopenia （42.9%）, nausea and vomiting （ 33.9 % ）, and oral cavity mucosal ulcer （ 100% ）. Conclusions： The combination of radiotherapy and chemotherapy plus H101 injection possessed a distinct efficacy in patients with nasopharyngeal carcinoma with lower toxicities. It may become a new pattern of comprehensive therapy for nasopharyngeal carcinoma. The long-term effect need to be further investigated.