Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): results of phase I and II trials.
Replication-selective viral agents hold promise as a novel cancer treatment platform (virotherapy). dl1520 (Onyx-015, now CI-1042, Pfizer Corp., Groton, CT, USA), an E1B-55kD gene-deleted adenovirus, was the first such genetically engineered agent to be tested in humans. Over 250 cancer patients have now been treated on approximately ten clinical trials (phase I-III). The virus was generally well tolerated at doses of up to 2 x 10(12) particles by intratumoural, intraperitoneal, hepatic arterial and i.v. administration; no maximally-tolerated doses were identified following intra-vascular administration. Viral replication was tumour-selective and was documented after administration by all routes; however, viral replication was variable depending on tumour histology. Single agent efficacy has been relatively limited to date (0-14% local tumour regression rates). In combination with chemotherapy, however, encouraging antitumoural activity has been demonstrated. These clinical research results demonstrate the potential of this novel treatment platform, as well as the hurdles to be overcome. Novel replication-selective agents with improved potency are being developed.
Kirn
D
D
Viral and Genetic Therapy Programme, Imperial Cancer Research Fund, Molecular Oncology Unit, Hammersmith Hospital, London, UK. d.kirn@icrf.icnet.uk
D000256:Adenoviridae / Q000235:genetics*; D002986:Clinical Trials as Topic; D003673:Defective Viruses; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D014779:Virus Replication