TREATMENT OF HEPATOCELLULAR-CARCINOMA - A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS

Background: Hepatocellular carcinoma (HCC) is a leading cause of cance r-related death. Many treatments have been proposed but considerable u ncertainty 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 treatmen ts 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 probabili ty of surviving up to one year was calculated according to the Mantel- Haenszel-Peto method and displayed using l'Abbe plots. Results: The 37 RCTs overall included 2803 patients (median 56, range 20-289). Patien ts 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 regim ens of intravenous or intraarterial chemotherapy with or without embol ization of hepatic artery, hormone- and immunotherapy regimens. Some e vidence of a moderate benefit emerged only from RCTs using tamoxifen a nd transcatheter arterial embolization vs. no treatment in unresectabl e 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 si gnificant for tamoxifen 1.2 (95% CI 0.6-2.6) but was significant for e mbolization 2.3 (95% CI 1.2-4.6). No evidence of efficacy was detected for embolization as adjuvant therapy in resected or transplantated pa tients nor for chemotherapy added to intraarterial embolization. Concl usions: This systematic review of RCTs on HCC, mostly in non resectabl e patients, indicate that the non-surgical current treatments are inef fective or minimally and uncertainly effective. The three treatment mo dalities minimally and uncertainly effective (i.e., embolization, tamo xifen and IFN) can deserve further assessment by larger and methodolog ically more sound randomized trials.