[Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in combination with chemotherapy in patients with cancer].
ABSTRACT In recent years,great development have been made in cancer therapeutics with replication-competent viruses (oncolytic viruses), E1B deleted adenovirus is one of promising viruses. The current study was designed to evaluate the efficacy and toxicity of intratumoral H101, a E1B-deleted adenovirus, in combination with chemotherapy on patients with cancer.
A total of 50 patients with malignant tumors in multiple centers clinical trial were treated with H101, 0.5ml 5x10(11) viral particle per day for 5 consecutive days every three weeks. Routine chemotherapy was performed at the same time. And the efficacy and toxicity were recorded.
Among 46 valuable cases, the overall response rate was 30.4%. The response rate was 28.0% (14/50) among ITT population, including 3 complete response (CR) and 11 partial response (PR). The overall response rate of control lesion was 13.0%, including 1 case of CR and 5 cases of PR. Thus, the response rate in injected lesion is clearly higher than that in control lesion (P< 0.001). Main side effects were injection site pain (26.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients, grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities were found in 4 patients.
The study showed that the combination of genetically modified adenovirus (H101) and chemotherapy possessed some effect for treating the patients with refractory malignant tumors, and the toxicities were lower, well tolerated.
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ABSTRACT: Since the 1990s, oncolytic viruses were utilized to treat cancer patients from phase I to phase III. Oncolytic virus development in China has been keeping in step with that in other countries and even accelerated the process in some fields, especially in conducting clinical trials. H101 is one kind of oncolytic adenovirus with E1B-55KD and partial E3 deleted developed by Shanghai Sunwaybio. From 2000-2004, phase I to phase III clinical trials for treating head and neck cancer were conducted in China. Clinical data show that H101 is well tolerable and has good efficacy when combined with chemotherapy in some cancer treatment modalities. We review the clinical results and relative issues of H101 in treating cancer and discuss approaches and possible improvements for the future. Information on other oncolytic viruses developing in China is also provided.Current cancer drug targets 04/2007; 7(2):141-8. · 5.13 Impact Factor
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ABSTRACT: It has been 9 years since the beginning of the first clinical trial in which an oncolytic virus was administered to cancer patients. Since then, oncolytic viruses from five different species have been taken to phase I and II clinical trials in over 300 cancer patients. While additional studies will be required to ascertain if the efficacy of any of these agents is high enough to warrant adding them to the existing therapeutic regimen, it has been reassuring that DNA viruses engineered to achieve tumor selectivity and RNA viruses with relative inherent natural tumor selectivity have proven reasonably safe at the wide range of doses that were tested. Here, we review the biology and clinical results of these five species of viruses and discuss lessons learned and challenges for the future.Oncogene 12/2005; 24(52):7802-16. · 7.36 Impact Factor
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ABSTRACT: Head and neck cancers usually present with advanced disease and novel therapies are urgently needed. Genetic therapy aims at restoring malfunctioned tumor suppressor gene(s) or introducing proapoptotic genes. Oncolytic virotherapeutics induce multiple cycles of cancer-specific virus replication, followed by oncolysis, virus spreading and infection of adjacent cancer cells. Oncolytic viruses can also be armed to express therapeutic transgene(s). Recent advances in preclinical and clinical studies are revealing the potential of both therapeutic classes for advanced head and neck cancers, including the approval of two products (Gendicine and H101) by a governmental agency. This review summarizes the available clinical data to date and discusses the challenges and future directions.Drug discovery today 07/2009; 14(11-12):570-8. · 6.63 Impact Factor