Annals of Oncology 8:117-136, 1997
© 1997 European Society for Medical Oncology
review-article |
Treatment of hepatocellular carcinoma: A systematic review of randomized controlled trials
1Divisione di Medicina, Ospedale V. Cervello Palermo, Italy
2Laboratorio di Epidemiologia Clinica, Istituto M Negri Milan Italy
3Istituto di Medicina Generale e Pneumologia, Università di Palermo Italy
Correspondence to: Dr. R. G. Simonetti Divisione Medicina Interna Ospedale Cervello Via Trabucco 180 90146 Palermo, Italy
BACKGROUND:: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Many treatments have been proposed but considerable uncertainty still remains about their effectiveness. In this review we evaluated the quality, clinical coherence, consistency and results of Randomized Controlled Trials (RCT) of non-surgical treatments for HCC.
METHODS:: Thirty-seven RCTs examining the effect of different treatments were retrieved using MEDLINE (November 1978 to December 1995) and a review of reference lists. Selected aspects of the quality of design, conduct and reporting were examined. The odds ratio for the probability of surviving up to one year was calculated according to the Mantel-Haenszel-Peto method and displayed using l'Abbé plots.
RESULTS:: The 37 RCTs overall included 2803 patients (median 56, range 20-289). Patients prognosis varied widely across studies which also failed to report on important information about their characteristics. Only 10 RCTs had an untreated control group; the remaining 27 compared different regimens of intravenous or intraarterial chemotherapy with or without embolization of hepatic artery, hormono- and immunotherapy regimens. Some evidence of a moderate benefit emerged only from RCTs using tamoxifen and transcatheter arterial embolization vs. no treatment in unresectable patients: pooled odds ratio for 1-year survival were, respectively, 2.0 (95% confidence intervals (CI) 1.1–3.6) and 2.0 (95% CI 1.1–3.6). At 2 years, however, pooled odds ratio were no longer statistically signscant for tamoxifen 1.2 (95% CI 0.6–2.6) but was significant for embolization 2.3 (95% CI 1.2–4.6). No evidence of efficacy was detected for embolization as adjuvant therapy in resected or transplantated patients nor for chemotherapy added to intraarterial embolization.
CONCLUSIONS:: This systematic review of RCTs on HCC, mostly in non resectable patients, indicate that the non-surgical current treatments are ineffective or minimally and uncertainly effective. The three treatment modalities minimally and uncertainly effective (i.e., embolization, tamoxifen and IFN) can deserve further assessment by larger and methodologically more sound randomized trials.
hepatocellular carcinoma, meta-analysis, randomized controlled trials, treatment
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