A Phase II Study of Tegafur/Uracil (UFUR®)Plus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma (HCC)

Inclusion Criteria:

1. Histologically proven HCC, or HCC diagnosed by clinical criteria. The clinical diagnosis of HCC should is defined when all the following criteria are met:

   I.Chronic hepatitis B or C virus carrier; II.Presence of hepatic tumor(s) with image findings (sonography, CT scan, etc) compatible with HCC and no evidence of other gastrointestinal tumors; III.A persistent elevation of serum α-fetoprotein (AFP) level of ≧ 400 ng/ml.
2. Stage IV diseases by AJCC staging system, or loco-regional diseases which are not operable and not treatable by transarterial (chemo)embolization, percutaenous interventional therapy, or other empirical therapy of higher priority.
3. Measurable disease by RECIST criteria.
4. Karnofsky performance status ≧ 70%.
5. Age of 18 years or older.
6. Adequate liver function reserves:

   I.Class A according to Child-Pugh classification; II.Alanine aminotransferase (ALT) ≦ 5 times the ULN; III.Serum total bilirubin ≦ 1.5 times ULN.
7. Adequate bone marrow reserves:

   White blood cell (WBC) ≧ 4,000/mm3 or absolute neutrophil count (ANC) ≧ 1,500/mm3;Platelets ≧ 75,000/mm3.
8. Serum creatinine ≦ 1.5 times the ULN.
9. Previous local therapy, such as radiotherapy, hepatic arterial embolization, radiofrequency ablation, percutaenous inverventional therapy, is allowed if the treatment was completed at least 6 weeks prior to the enrollment.
10. Sexually active patients, in conjunction with their partners, must practice birth control during and for 3 months after thalidomide therapy.
11. Written informed consent.

Exclusion Criteria:

1. Concurrent radiotherapy, chemotherapy, immunotherapeutic drugs, corticosteroids or other investigational drug(s).
2. Previous exposure to the followings:

   I.Cytotoxic chemotherapy; II.Thalidomide.
3. CNS metastasis.
4. Concomitant diseases that might be aggravated by investigational drugs:

   I.Active or non-controlled infection; II.≧ NCI grade 2 peripheral neuropathy; III.History of seizures within the past 10 years or currently on anticonvulsant medication.
5. Organ transplantation.
6. Major systemic diseases those are inappropriate for systemic chemotherapy.
7. Mental status not fit for clinical trials.
8. Inability to take medications orally.
9. Pregnant or breast-feeding women.
10. Life expectancy less than 3 month.
11. Other malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ, from which the patient has been disease-free for 5 years.