Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Nov 19:5:109-119.
doi: 10.2147/JHC.S169285. eCollection 2018.

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

Hamdy A Azim  1 , Ashraf Omar  2 , Hesham Atef  1 , Heba Zawahry  3 , Mohamed K Shaker  4 , Ah Kamel Abdelmaksoud  5 , Mohamed EzzElarab  6 , Omar Abdel-Rahman  7 , Mohamed Ismail  8 , Loay Kassem  1 , Imam Waked  9
Affiliations

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

Hamdy A Azim et al. J Hepatocell Carcinoma. .

Abstract

Background: Phase 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.

Methods: Patients 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).

Results: Between 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).

Conclusion: In patients with advanced HCC, adding UFT to sorafenib is feasible, but it did not improve efficacy outcome over sorafenib monotherapy.

Keywords: Egypt; advanced hepatocellular carcinoma; sorafenib; tegafur/uracil.

PubMed Disclaimer

Conflict of interest statement

Disclosure IW received grants/research supports from: Abbvie, Gilead, Janssen, Pharco, Mylan, Onxio and participated in company sponsored speaker’s bureau of Abbvie, Eva-Pharma, Gilead, Janssen, Marcyrl, Mylan, and Roche. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for TTP (A), PFS (B), and OS (C) across the two treatment arms (combination arm in blue vs sorafenib alone in red). Abbreviations: OS, overall survival; PFS, progression free survival; TTP, time to progression; UFT, tegafur–uracil.
Figure 2
Figure 2
A graphical representation of the change in the mean of the EQ-5D score (A) and the FHSI-8 score (B) for sorafenib only (red) vs sorafenib+ UFT (blue) spanning from the start of cycle 1 (pretreatment) to the start of cycle 4. Notes: (A) Patients in the sorafenib monotherapy arm had a non-significant decline in the general health QOL scores (EQ-5D) over the treatment period (P=0.21), while the sorafenib-UFT treated patients showed a significant deterioration of EQ-5D scores over the treatment period (P<0.001) and trended to have worse QOL parameters compared to the sorafenib-only group (P=0.158). (B) At the start of treatment, the mean of symptomatic burden (FHSI-8) among patients in the combination arm was less than that among patients in sorafenib monotherapy arm (P=0.186). At the start of cycle four and compared to baseline scores, patients in the two treatment groups experienced a significant deterioration of symptomatic burden scores, being more marked in patients in the combination arm (P<0.001 and P<0.01 for the combination arm and monotherapy arm, respectively). Abbreviations: EQ-5D, European Quality of Life–5 Dimensions; FHSI, Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index; QOL, quality of life; UFT, tegafur–uracil
See this image and copyright information in PMC

References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. - PubMed
    1. Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol. 2014;2014:437971. - PMC - PubMed
    1. Polaris Observatory HCV Collaborators Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017;2(3):161–176. - PubMed
    1. American Cancer Society A, Ga Cancer Facts and Figures, 2017. 2017. [Accessed April 2, 2017]. Available from: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts....
    1. Chlebowski RT, Brzechwa-Adjukiewicz A, Cowden A, Block JB, Tong M, Chan KK. Doxorubicin (75 mg/m2) for hepatocellular carcinoma: clinical and pharmacokinetic results. Cancer Treat Rep. 1984;68(3):487–491. - PubMed