The Further Clinical Research On The Targeting EBV-LMP1 Deoxyribozyme Enhancing The Radio-sensitivity Of Nasopharyngeal Carcinoma

ObjectiveNPC is the most common malignant epithelial carcinoma in South China. The NPC occurrence and the progression is closely related to EB virus. LMP1 is a oncogenic protein encoded by EB virus and promotes the invasion, metastasis and the resistance to the radiation therapy, which is the first line treatment to it. Thus the strategy to combine the gene therapy of this targeting LMP1 gene with radiotherapy is expected to enhance the local control and long term effect. We complied the DNAzymes targeting EBV-LMP1 to the EBV-LMP1 positive NPC patients, to observe the toxicity and the radio-sensitivity of the DNAzymes and the further control of the carcinoma.MethodsStrictly according to a certain requirement, a total of 40 NPC patients with the same histological type, poorly differentiated squamous carcinoma, and LMP1-lpositve were randomized into two groups, one treated by the combined therapy(radiation+DNAzymes),and another the radiation therapy all alone. A good performance status and a favorable hepatic and renal function are required, no matter with the gender or the age. The life expectancy was no shorter than at least 3 mouths. And it was the first time to adopt any treatments for them, and adjuvant or neo-adjuvant treatment or chemotherapy was not allowed in our schedule. They all arranged with radical radiation therapy over 7 weeks. We focus the toxicity on the impairment of hematological system which can directly indicate the proliferation of the hematological system, and on the function of the hepatic and renal and some other adverse reaction. The evaluation of the therapeutic effect on the local control and radio-sensitivity is the comparison of the RTR, efficiency multiplier of the RTR, overall survival and the time to progress, time to death.Results1. The general data is consistency, which means well homogeneity and balanced between 2 groups.2. There is no further toxicity to the hematological system and to the function of the hepatic and renal can be found between the 2 groups additional to the impairment of radiotherapy.3.At the 5th-week of the average RTR in the combined therapy group is 74.73%, while 64.89% in the radiotherapy only group, the Efficiency multiplier is 1.15, At the 7th-week of the average RTR is 88.01% in the combined therapy group, while 78.94% in the radiotherapy only group, the Efficiency multiplier is 1.11. At the 3rd-month after radiotherapy the average RTR in the combined therapy group is 98.64%,while 89.61% in the radiotherapy only group, the Efficiency multiplier is 1.10.While the PRTR3<0.05,which means the volume contraction in the combined therapy group is much distinct than another group. At the 7th-week of the radiotherapy, there are 7 patients got the complete remission, while only 1 patients in then radiotherapy only group 1; in 3-month after radiotherapy, the number of CR in combined therapy group was 2.2-times to the radiotherapy only group; Even in the PR team, the average RTR of the combined therapy group is better than radiation only group (1.13times), and PCR&PR=0.027<0.05, showing the effect of combined therapy group was significantly better in the recent radiotherapy.4. pos=0.692,pTTP=0.041,pTTD=0.102; 2-year survival rate is 85.7% in the combined treatment group, while 80.0% in the radiotherapy only group, while p1,2-year survival rate=0.737Conclusion1. DNAzymes targeting the EBV-LMP1 associated radio-therapy is of no additional toxicity to the LMP1-positive NPC patients.2. DNAzymes targeting the EBV-LMP1 can enhance the sensitivity of radio-therapy; it can increase of the rate of tumor regression.3. DNAzymes targeting the EBV-LMP1 associated radio-therapy can well control the progress.