Multicenter randomized phase III trial comparing tamoxifen alone or with transarterial lipiodol chemoembolization (TLC) for unresectable hepatocellular carcinoma (HCC) in cirrhotic patients

Abstract

4006 Background: Chemoembolization in the palliative treatment of HCC remains controversial. The FFCD 9402 multicenter phase III trial was designed to compare the effects of the association chemoembolization-tamoxifen (CT group) with tamoxifen alone (T group) on the overall survival (OS) and the quality of life (QoL). Methods: From 1995 to 2002, 138 patients were randomized between Tamoxifen (20 mg per day) with or without TLC with Epirubicin and stratified according to center and Okuda stage (I vs II). Among them 123 cirrhotic patients of Child-Pugh (CP) class A or B with unresectable HCC were eligible: 61 in the T group and 62 in the CT group. Analyses were performed in intent to treat with 5% type I and 20% type II error. Survival curves were estimated with Kaplan-Meir Method: OS was compared with Log-Rank test and multivariate Cox’s proportional hazards model. The Spitzer QoL index was longitudinally compared with a mixed model analysis of variance. Results: Baseline characteristics were similar: Child-Pugh class (71% A), etiology of cirrhosis (76% alcoholic), tumor stage (70% multinodular), Okuda stage (72% I) and unilobar portal vein obstruction (10%). In the CT group the mean courses per patient was 2.8 ± 2.3. At 2 years, the OS was respectively 22% and 25% in the T and CT groups (p=0.68). Multivariate analysis identified 4 significant prognostic factors: AFP > 400 ng/ml (p=0.007), hepatalgia (p=0.006), hepatomegaly (p=0.023) and < 6 included patients per center (p=0.032). The longitudinal QoL level did not differ (p=0.70). Among Okuda I, the 2 year-survival was respectively 28% in the T group and 32% in the CT group (p=0.58). The prognostic factors were similar to the whole population with moreover: Spitzer index (p<0.0001), male sex (p=0.008), and CP class (p=0.026). Conclusions: This study suggests that the TLC in the palliative treatment of HCC with cirrhosis did not improve the survival and the quality of life. No significant financial relationships to disclose.