A phase II study of sorafenib in combination with tegafur/uracil (UFT) for Asian patients with advanced hepatocellular carcinoma

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Author(s): Y. Shen, C. Hsu, C. Hsu, Z. Lin, P. Chen, Y. Shao, T. Huang, Y. Ding, A. Cheng; National Taiwan University Hospital, Taipei, Taiwan
 
Abstract:
Background:
Sorafenib, a multikinase inhibitor with antiangiogenic activity, has
recently been approved for the treatment of unresectable HCC.
Combination of sorafenib with metronomic chemotherapy has theoretic
advantage in improving antitumor activity without increasing
toxicities. UFT (tegafur: uracil = 4:1 in molar ratio), an oral
fluoropyrimidine, is active in various gastrointestinal cancers. We
conducted a phase II study to evaluate the efficacy and safety of
sorafenib plus low-dose UFT in advanced HCC patients (pts).
 
Methods:
Pts with histologically or cytologically proven unresectable/metastatic
HCC, ECOG PS 0-2, Child-Puch class A, platelets ? 100 K/µl,
transaminases ? 5 × ULN, bilirubin ? 3 mg/dl, INR ? 2.3 and creatinine
? 1.5 × ULN were enrolled. Prior systemic therapy for advanced disease
is not allowed. Sorafenib (400 mg bid) and UFT (125 mg/m2
based on tegafur bid) were taken per os continuously. Tumor assessment
was performed q8w by RECIST criteria. Primary endpoint is
progression-free survival (PFS).
 
Results: Between April 2007
and April 2008, 53 pts were enrolled. Baseline pts characteristics
were: M/F, 47/6; median age 57 (range, 31-83); CLIP score 0-3/4, 48/5;
extrahepatic spread/macroscopic vascular invasion, 33/30; and
HBsAg(+)/anti-HCV(+)/both(+), 38/13/4. 89% of pts were BCLC stage C.
Pts received a median of 3.7 (range 0.3- 18.9+) months of treatment.
There were 3 (6%) PR and 27 (51%) SD. The median PFS and OS were of 3.7
months (95% C.I., 1.9- 5.5) and 7.4 months (95% C.I., 3.4- 11.4),
respectively. Adverse events (AEs) were summarized in Table. Hand-foot
skin reaction (HFSR), fatigue, and diarrhea were most common AEs. HFSR
was the major AE resulting in dose reduction (19%) or treatment delay
(21%). Grade 3/4 neutropenia occurred in 2 pts (4%).
 
Conclusions:
Adding metronomic UFT chemotherapy to sorafenib may improve therapeutic
efficacy of the latter in pts with advanced HCC. The toxicity profile
of the combination is similar to that of sorafenib alone.