title: Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The prognosis of HCC is poor and current therapies are largely ineffective. Genetic abnormalities are commonly seen in HCC tumors particularly with inactivation of the p53 tumor suppressor. Gene therapy with E1B-deleted (dl1520) adenovirus could be of therapeutic value as it offers the potential of tumor growth control in patients with p53 mutation. Ten patients with posthepatitis cirrhosis and histologically proven HCC were enrolled into an open label, randomized prospective study. Randomization was to receive either percutaneous ethanol injection (control group) or dl1520. Toxicity and complications in the ethanol group were pain and fever, whereas in the gene therapy group complications were minimal. Grade I-II toxicity fever, stable performance status, and no significant rise in liver enzymes were observed in patients treated with dl1520. Analysis of patients' response to treatment in the gene therapy group showed one patient with a partial response and four patients with progressive disease. In the ethanol-treated group two patients had stable disease and three patients showed disease progression. In conclusion, this study showed that the adenovirus was well tolerated, but did not seem to offer significant tumor control. Although only a small number of patients were treated here it appears that more effective vectors are needed to achieve a useful clinical impact.
authors.affiliation: Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital Campus, London W12 ONN, UK. nagy.habib@ic.ac.uk
authors.forename: Nagy
authors.initials: N
authors.lastname: Habib
authors.forename: Hosny
authors.initials: H
authors.lastname: Salama
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abd El Latif Abu Median
authors.forename: Ilia
authors.initials: I
authors.lastname: Isac Anis
authors.forename: Rasha Ahmed
authors.initials: RA
authors.lastname: Abd Al Aziz
authors.forename: Catherine
authors.initials: C
authors.lastname: Sarraf
authors.forename: Ragai
authors.initials: R
authors.lastname: Mitry
authors.forename: Roman
authors.initials: R
authors.lastname: Havlik
authors.forename: Prem
authors.initials: P
authors.lastname: Seth
authors.forename: Jack
authors.initials: J
authors.lastname: Hartwigsen
authors.forename: Reva
authors.initials: R
authors.lastname: Bhushan
authors.forename: Joanna
authors.initials: J
authors.lastname: Nicholls
authors.forename: Steen
authors.initials: S
authors.lastname: Jensen
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy* / Q000648:ultrastructure; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology / Q000628:therapy; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D017501:Adenovirus E1B Proteins; D000431:Ethanol