Clinical Observation Of Recombinant Human Adenovirus-p53Injection Combined With Standard Therapy For Malignant Glioma

CNS glioma is the most common type of brain tumor, accounted for about half ofprimary brain tumor, of which more than70%of glioma is malignant glioma[1].According to the content which tumor professional group of neurosurgery department ofChinese Medical Association in2009for "Chinese consensus for diagnosis andtreatment of central nervous system malignant glioma" strongly recommended,standardization of treatment strategies for malignant glioma are maximum safe resectionof the tumor, postoperative concurrent chemoradiotherapy and adjuvant chemotherapy[2].However, the prognosis of malignant glioma remains poor. In recent years, more andmore experiments show that gene therapy can be combined with standard treatmentstrategies to improve the prognosis of patients of malignant glioma. As a specialtechnology of gene therapy, rAd-p53has been widely used in solid tumor. The principleof its treatment is transduction of wild type p53gene into tumor cells by adenovirus,P53protein encoded by p53gene could be expressed in tumor cells, thus changed thebiological behavior of low differentiation, high proliferation and anti-apoptosis causedby the dysfunction of P53protein, eventually killing tumor cells. In addition, theexpression of P53protein can effectively "wake up" the immune responses whichagainst tumor, and block tumor angiogenesis through the powerful "bystander effect" toinhibit the tumor vascular epithelial growth factor. What’s more, the strategy ofrAd-p53combined with standard treatment strategies for cancer can improve thesensitivity of both chemotherapy and radiotherapy. At present, rAd-p53has beenapplied to clinical treatment for cancer of head and neck, lung, digestive system, urinarysystem and gynaecology.Objective：Observe the clinical effect and adverse reaction of rAd-p53combinedwith standard treatment strategies for malignant glioma of the central nervous system and to explore its clinical application value.Method： From October2011to March2013,5patients in department ofneurosurgery, General Hospital of Shenyang Military Command with malignant gliomathat p53gene mutation received standard therapy combined with recombinant humanadenovirus-p53injection, among them4cases received Ommaya injection for rAd-p53therapy,1case received intravenous drip. The clinical efficacy of patients aftertreatment and3months after treatment judged with response evaluation criteria in solidtumors. The quality of life of patients after treatment was evaluated by KPS. Theadverse reaction during treatment evaluated in WHO Toxicity of anticancer drugsclassification criteria.Results：Among5cases, there were3cases of complete remission,2case ofpartial remission,2cases of complete remission,2cases of partial remission. Thequality of life was improved in3cases，stabled in1case，and decreased in1case. Themain adverse reactions were fever, nausea and vomiting, symptomatic treatment couldimprove them.Conclusion： rAd-p53combined with standard therapy in malignant glioma hassome clinical effect. To a certain extent, it can improve the quality of life of patients,with less adverse reactions. It is necessary to design further clinical trial for certain theclinical effectiveness of rAd-p53combined with standard therapy for malignant glioma.