Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma.
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.
Habib
Nagy
N
Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital Campus, London W12 ONN, UK. nagy.habib@ic.ac.uk
Salama
Hosny
H
Abd El Latif Abu Median
Ahmed
A
Isac Anis
Ilia
I
Abd Al Aziz
Rasha Ahmed
RA
Sarraf
Catherine
C
Mitry
Ragai
R
Havlik
Roman
R
Seth
Prem
P
Hartwigsen
Jack
J
Bhushan
Reva
R
Nicholls
Joanna
J
Jensen
Steen
S
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
D017501:Adenovirus E1B Proteins; D000431:Ethanol