重组人p53腺病毒注射液联合放射线治疗头颈鳞癌的Ⅱ期临床试验

目的　评价重组人p5 3腺病毒注射液 (rAd p5 3)联合放射线治疗头颈鳞癌的疗效及安全性。方法　自 2 0 0 1年 10月至 2 0 0 2年 9月 ,对 4 2例头颈鳞癌进行了rAd p5 3制剂结合放疗 (基因治疗加放疗 ,GTRT)对比单纯放疗 (单纯放疗 ,RT)的前瞻性随机对照Ⅱ期临床试验。患者被随机地分入结合治疗的GTRT组 (共 2 0例 )和作为对照的RT组 (共 2 2例 )。在GTRT组 ,每周 1次行瘤内注射rAd p5 3制剂 1× 10 1 2 病毒颗粒共 8次 ,同时结合放疗。两组都采用同样的常规放疗方案 ,每次 2Gy ,每周 5次 ,使原发灶和颈部转移淋巴结都达到 70Gy 35f 7～ 8w。观测病人的不良反应、血清抗腺病毒抗体水平和肿瘤变化。以CT对比分析GTRT组和RT组病人在 4 0Gy、70Gy及疗效确认时 (治疗后 2月 )肿瘤即刻反应率。结果　随机对比分析或自身对比分析结果都表明 ,rAd p5 3明显地提高了头颈鳞癌患者放疗的疗效 (P <0 0 5 )。随机对比结果表明 ,rAd p5 3对 4 0Gy放疗的增效倍数为 1 72 ,疗效确认时头颈鳞癌GTRT组CR率比RT组CR率提高 1 6 8倍。自身对比结果表明 ,rAd p5 3对 4 0Gy放疗的增效倍数为 1 6 9,疗效确认时头颈鳞癌GTRT瘤灶的CR率比自身RT瘤灶CR率提高 2 5 3倍。 2 0例头颈鳞癌患者接受多次rAd p5 3瘤内注射 ,除了出现一时性

Treatment of head and neck squamous cell carcinoma by recombinant adenovirus-p53 combined with radiotherapy: a phase II clinical trial of 42 cases

OBJECTIVE: To evaluate the efficacy and safety of recombinant adenovirus-p53 (Adp53, SBN-1) combined with radiotherapy in treatment of head and neck squamous cell carcinoma (HNSCC). METHODS: Forty-two patients with HNSCC were randomly divided into 2 groups: gene therapy + radiotherapy group (GTRT group. n = 20, SBN-1 solution 1 x 10(12) VP was injected intratumorally once a week for 8 weeks and radiotherapy was begun since the 3rd day of gene therapy 5 fractions a week with the with the fraction dosage of 2 Gy and total dosage of 70 GY) and radiotherapy group (RT group. n = 22, the above regimen of radiotherapy was conducted). CT was conducted 5 weeks and 8 weeks after the beginning of treatment and 2 months after the finish of treatment (validation point) to calculate the size of tumor. Patients were monitored for adverse event and serum level of anti-adenoviral antibody. A comparative study was also performed on the immediate response rate by CT at the times when the dosages of 40 Gy and 70 Gy had been given. RESULTS: The average tumor reduction rates were (63 +/- 17)%, (82 +/- 18)%, and (90 +/- 16)% at the 40 Gy time point, 70 Gy time point, and validation point respectively in the GTRT group, all higher than those in the RT group (37 +/- 26)%, (62 +/- 39)%, and (70 +/- 34)% respectively, all P < 0.05. Random control study showed that the radio-sensitized enhancement rate was 1.72 at 40 Gy time point and the CR rate of the GRTR group at the validation point was 1.68 times higher than that of the RT group. Self-controlled study showed that the SBN-1 radio-sensitized enhancement ratio in the 4 GTRT group was 1.69 at 40 Gy time point and the CR rate of the GTRT group at validation point was 253% that of the RT group (P < 0.01). No dose-limiting toxicity and adverse events were noted, except transient fever after SBN-1 administration. CONCLUSION: A potentially effective gene therapeutic agent for HNSCC treatment, intratumoral injection of SBN-1 is safe.