重组人p53腺病毒注射液结合放射治疗鼻咽癌Ⅱ期临床试验观察

Recombinant adenovirus p53 agent injection combince with radiotherapy in treatment of nasopharyngeal carcinoma: a phase Ⅱ clinical trial

目的 观察重组人p5 3腺病毒注射液 (rAd p5 3)配合放疗治疗鼻咽癌 (NPC)的疗效及毒性反应。方法 2 9例鼻咽鳞癌随机分成基因治疗 +放疗组 (GTRT) 16例和单纯放疗组 (RT) 13例。GTRT组患者应用rAd p5 3瘤内注射 1次 周× 8,放疗在rAd p5 3注射 3d后开始。两组放疗剂量和方法相同。结果 采用rAd p5 3注射液治疗 4周后 ,两组肿瘤平均缩小率分别为 71%± 18%和 4 9%±2 3% (P <0 0 0 1)。治疗 8周后 ,两组肿瘤平均缩小率分别为 95 %± 10 %和 80 %± 17% (P <0 0 0 1)。治疗结束 4周后 ,两组肿瘤完全消退率分别为 75 %和 15 % (P <0 0 1)。GTRT组有 3例患者治疗过程中出现自限性低热 ,余无明显毒副反应。结论 rAd p5 3配合放疗治疗NPC具有较好疗效 ,临床使用安全 ,不良反应轻微。

Objective To evaluate the efficacy and toxicity of recombinant adenovirus p53 agent (SBN-1) combined with radiotherapy in treatment of nasopharyngeal carcinoma. Methods Twenty-nine cases with nasopharyngeal carcinoma were randomly divided into two groups: gene therapy + radiotherapy group (GTRT group, n=16, SBN-1 was injected intratumorally once a week for 8 weeks, and radiotherapy with the dosage of 60～70 Gy was given 3 days after the first injection of SBN-1) and radiotherapy group (RT group, n=213, the same regimen of radiotherapy was given only). CT and MRI were conducted 4, 8, and 12 weeks after to evaluate the size of tumor. Then the patients were followed-up every month. Toxicity was evaluated by physical examination, KPS scoring, blood, urine, and feces routines, serum BUN, creatine, AST, ALT, LDH, and AKP, electrocardiography, and X-ray. Results The tumors of the patients group were reduced by 70.9±18.1% and 49.4±22.8% in the GTRT group and the RT group respectively (P<0.001) 4 weeks after treatment; and were reduced by 94.9±10.2% and 80.4±17.0% in the GTRT group and RT group respectively (P<0.001) 8 weeks after treatment. The rates of complete regression of tumor 12 weeks after the treatment were 75% and 15% in the GTRT group and RT group respectively (P<0.005). 3 cases presented mild, self-limited fever and no other side effects were noted. Conclusion Local injection of SBN-1 combined with radiotherapy to treat nasopharyngeal carcinoma is safe and significantly more effective than single radiotherapy.