重组腺病毒-p53联合放疗治疗头颈部鳞状细胞癌：42例II期临床试验

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

作者信息

Zhang Shan-wen, Xiao Shao-wen, Liu Chang-qing, Sun Yan, Su Xing, Li Dong-ming, Xu Gang, Cai Yong, Zhu Guang-ying, Xu Bo, Lü You-yong

机构信息

Department of Radiotherapy, Beijing University School of Oncology, Beijing 100036, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2023-8.

PMID:14703408

Abstract

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.

摘要

目的

评估重组腺病毒-p53（Adp53，SBN-1）联合放疗治疗头颈部鳞状细胞癌（HNSCC）的疗效和安全性。

方法

42例HNSCC患者随机分为2组：基因治疗+放疗组（GTRT组，n = 20，每周1次瘤内注射SBN-1溶液1×10(12)病毒粒子，共8周，自基因治疗第3天开始放疗，每周5次，每次剂量2 Gy，总剂量70 Gy）和放疗组（RT组，n = 22，采用上述放疗方案）。治疗开始后5周、8周及治疗结束后2个月（验证点）行CT检查以计算肿瘤大小。监测患者不良事件及血清抗腺病毒抗体水平。在给予40 Gy和70 Gy剂量时，通过CT对即时反应率进行比较研究。

结果

GTRT组在40 Gy时间点、70 Gy时间点及验证点的平均肿瘤缩小率分别为(63±17)%、(82±18)%和(90±16)%，均高于RT组的(37±26)%、(62±39)%和(70±34)%，差异均有统计学意义（P < 0.05）。随机对照研究显示，40 Gy时间点放射增敏增强率为1.72，GTRT组在验证点的完全缓解（CR）率比RT组高1.68倍。自身对照研究显示，GTRT组在40 Gy时间点SBN-1放射增敏增强比为1.69，GTRT组在验证点的CR率是RT组的253%（P < 0.01）。除SBN-1给药后出现短暂发热外，未观察到剂量限制性毒性和不良事件。