Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned?
Replication-selective microbial agents hold promise as a novel cancer treatment platform. dl1520 (Onyx-015), an E1B-55 kD gene-deleted adenovirus, was the first such genetically engineered agent to be tested in humans. Over 200 cancer patients have been treated to date on over 10 clinical trials (phases I-III). The virus was generally well-tolerated at doses of up to 2 x 10(12) particles by intratumoral, intraperitoneal, hepatic arterial and intravenous administration; no maximally tolerated doses were identified by any route of administration. Viral replication was tumor-selective, and was documented after administration by all routes; replication was generally transient (<10 days), however, and was variable depending on tumor histology. single agent efficacy has been limited to date (0-14% local tumor regression rates). in combination with chemotherapy, however, encouraging antitumoral 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 needed.
Kirn
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Viral and Genetic Therapy Programme, Imperial College School of Medicine, Imperial Cancer Research Fund, Molecular Oncology Unit, Hammersmith Hospital, London W12 0NN, UK.
D000256:Adenoviridae / Q000235:genetics* / Q000254:growth & development; D002986:Clinical Trials as Topic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D014779:Virus Replication