Review article: Overview of medical treatments in unresectable hepatocellular carcinoma--an impossible meta-analysis?
BACKGROUND
Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist.


OBJECTIVE
To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials.


METHODS
Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen.


RESULTS
Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference -3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference -2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1-18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = 0.9-6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0-49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant.


CONCLUSIONS
No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.
Service d'Hépatogastroentérologie, Hôpital Pitié-Salpêtriere, Paris, France.
P
P
Mathurin
O
O
Rixe
N
N
Carbonell
B
B
Bernard
P
P
Cluzel
M F
MF
Bellin
D
D
Khayat
P
P
Opolon
T
T
Poynard
D000279:Administration, Cutaneous; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000628:therapy; D004317:Doxorubicin / Q000627:therapeutic use; D000431:Ethanol / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000628:therapy; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use
D000970:Antineoplastic Agents; D013629:Tamoxifen; D000431:Ethanol; D004317:Doxorubicin; D007372:Interferons; D005472:Fluorouracil