A phase II trial of thalidomide plus tegafur/uracil for patients with advanced/metastatic hepatocellular carcinoma (HCC)

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Author(s): C. Hsu,
Z. Lin, K. Lee, K. Yeh, C. Hsiao, Y. Shen, D. Chang, S. Wang, C. Hsu,
A. Cheng; National Taiwan University Hospital, Taipei, Taiwan; Chia-Yi
Chang Gung Memorial Hospital, Chia-Yi, Taiwan; Far Eastern Memorial
Hospital, Taipei, Taiwan
Background: Thalidomide
(T) is an anti-angiogenic agent with modest activity in
advanced/metastatic HCC. Tegafur/uracil (UFT) is an oral prodrug of
5-fluorouracil with activity against various gastrointestinal cancers.
Metronomic chemotherapy has been shown to have anti-angiogenic and
anti-cancer effect in preclinical and clinical models. This study
evaluated the efficacy and safety of the combination of T and
metronomic UFT as first-line therapy for advanced HCC.
Methods: Patients (Pts) with advanced HCC not treatable by surgery or other loco-regional therapies received T 100mg bid and UFT 125mg/m2
(based on tegafur) bid continuously. Treatment was continued in the
absence of disease progression or unacceptable toxicity. Primary
endpoint was response rate (RR) by RECIST; secondary endpoints were
disease control rate (CR+PR+SD), progression-free survival (PFS),
overall survival (OS), and safety.
Results: Between Jul 2006
and Jul 2008, 43 intent-to-treat pts (M/F 41/2, median age 55) were
enrolled. Baseline characteristics were HBsAg(+)/anti-HCV(+)/both(+)
/both(-) 31/6/1/7; AJCC stage II/III/IV 2/18/23; BCLC stage B/C 1/42;
CLIP score ?3/4 27/16; portal vein thrombosis 65%; extrahepatic
metastasis 58%; prior local treatment 72%. There were 4 PR (9.3%) and
10 SD (23.3%), with a disease control rate of 32.6%. Median OS was 4.6
(95% CI, 3.5-7.3) months and median PFS was 1.9 (95% CI, 1.8-2.6)
months. The OS and PFS for pts with CLIP score ?3 were 7.6 and 2.6
months, respectively. Grade 3 leucopenia developed in 1 (2.3%) pt. The
most common treatment-related grade 3 non-hematologic toxicities were
somnolence (n=4, 9.3%), GI bleeding (n=3, 7.0%), and elevated
transaminase (n=2, 4.7%). No grade 4 toxicities occurred.
The combination of T with metronomic UFT is a well-tolerated regimen
with moderate activity for advanced HCC, and worth further exploration
in pts with CLIP score ?3.