Sorafenib plus tegafur–uracil (UFT) versus sorafenib as first line systemic treatment for patients with advanced stage HCC: a Phase II trial (ESLC01 study)

Abstract

BackgroundPhase II trials found that tegafur–uracil (UFT) is an effective drug in hepatocellular carcinoma (HCC), while preclinical data suggested that its combination with sorafenib may have a promising activity. Our Phase II randomized trial aimed to evaluate efficacy and tolerability of sorafenib plus UFT vs sorafenib in advanced HCC.MethodsPatients with advanced HCC, with no prior systemic therapy, were randomized to receive either UFT at 125 mg/m2 twice daily for 4 out of 5 weeks plus sorafenib at 400 mg twice daily (arm 1) or single agent sorafenib at 400 mg twice daily (arm 2). Primary end point was time to progression (TTP).ResultsBetween March 2012 and March 2014, 76 eligible patients – out of 143 preplanned – were randomized. The study was terminated early because of futility. This is the final analysis of the study, after a median follow-up of 10.2 months and death of 86% of randomized patients (n=64). Median TTP was 7.5 months and 8.2 months in arms 1 and 2 respectively (HR: 1.07; 95% CI, 0.52–2.22; P=0.855), while the median overall survival was 8.2 months and 10.5 months respectively (HR: 1.58; 95% CI: 0.90–2.76, P=0.112). Nine patients (25%) in the combination arm discontinued treatment because of toxicity vs eight patients (21.1%) in the sorafenib monotherapy arm (P=0.899).ConclusionIn patients with advanced HCC, adding UFT to sorafenib is feasible, but it did not improve efficacy outcome over sorafenib monotherapy.

Exosomes and Hepatocellular Carcinoma: From Bench to Bedside

“…Patients treated with sorafenib also acquired resistance [24] and suffered from adverse events [25]. Many trials evaluating systemic chemotherapy in patients with advanced HCC are ongoing [26,27,28].…”

Association between miR-196a2 polymorphism and the development of hepatocellular carcinoma in the Egyptian population

“…The incidence of liver cancer is one of the highest cancers in Egypt, also it is the fifth most common cancer in both genders and the prognosis for patients with HCC is generally poor [8]. So, early diagnosis of HCC is mandatory for the development of specific curative therapies.…”

Targeted therapy for hepatocellular carcinoma

“…Sorafenib has been combined with anti-angiogenic agents, MEK/ERK pathway inhibitors, mTOR pathway inhibitors, histone deacetylase inhibitors, EGF/EGFR pathway inhibitors, and HGF/c-Met pathway inhibitors. 31 Other agents such as interferon, 32 selumetinib, 33 capecitabine, 34 tegafur-uracil, 35 gemcitabine and oxaliplatin (GEMOX), 36 , 37 and gemcitabine alone 38 have also been evaluated but to date no treatments involving combinations containing sorafenib have succeeded in phase III trials.…”