Preliminary Assessment On The Safety And Clinical Efficacy Of An Oncolytic Adenovirus To Patients With Solid Tumors

Objective: To investigate the safety and clinical efficacy of Ad-ETK, an oncolytic adenovirus encoding suicide gene (TK gene), to treat patients with solid tumors.Methods: Ten patients with advanced solid tumors, in whom the conventional therapies were used to be given were invalidly or lost, were rolled up in this study upon signing informed consent. According to different solid tumors, The Ad-ETK were administrated via various routes including four patients were administrated by percataneously femoral arteriopuncture to intervene into the tumor vessel, four patients were administrated by CT-guided local puncture injection, and two with malignant ascites were administrated by intraperitoneal perfusion. The doses of Ad-ETK were 1⁵×10¹⁰ pfu every time, and 3⁶ times as a course of treatment. 0.25g of ganciclovir (GCV) twice a day for 3 days was intravenously administrated 24 h after given Ad-ETK. The all kinds of adverse events were monitored based on the Common Terminology Criteria for Adverse Events v3.0 (CTCAE), established by the National Cancer Institute (NCI), and the clinical efficacy of Ad-ETK was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST).Results: The common side effects after the administration of Ad-ETK was influenza-like symptoms, including rigors, fever, fatigue, and muscular soreness. The frequence was associated with the route of administration, in which the side effects by percataneous femoral arteriopuncture had the most incidence, next by CT-guided percutaneously intratumoral injection and direct intraperitoneal injection, respectively. The function of important organs such as the heart, liver, and kidney had no obvious damage in the period of the treatment of Ad-ETK. In the ten patients, the treatment of Ad-ETK resulted in volume of tumor shrink in various degrees imaged by CT in six patients, lead to an amount of ascites significant reduction and CA125, a blood tumor marker, decrease in one with ovarian cancer accompanied by heavy malignant ascites.Conclusion: Good safety of Ad-ETK is shown by the administrations of multiple routs, and common side effects have wild and mild influenza-like symptoms, of which the patients can be well tolerated. In addition, the Ad-ETK treatment made some benefit to the patients with advanced-stage solid tumors.