Adjuvant Therapy of Gefitinib (Iressa, ZD1839) in Patients With Resectable Hepatocellular Carcinoma
Adjuvant Therapy of Gefitinib (Iressa, ZD1839) in Patients With Resectable Hepatocellular Carcinoma
This research is being done to find how soon the liver cancer may come back and whether
 proteins or genes in tumor, blood or urine can give us clues of early recurrence.
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world1. HCC risk
 increases drastically in patients with chronic hepatitis B infection, hepatitis C infection
 or liver cirrhosis. HCC is very prevalent in our region due to endemic hepatitis B infection
 and increasing incidence of hepatitis C.

 Patients with HCC have very poor prognosis because HCC tumors are usually non-symptomatic.
 Most patients will not be diagnosed until the disease has reached an advanced stage.
 Chemotherapy may offer palliative benefit to some patients with advanced HCC but has not been
 shown to prolong survival in these patients. HCC patients are in need for innovative and
 targeted therapies. Therefore, we propose to study gefitinib as an adjuvant therapy in
 patients with resected HCC.

 Gefitinib blocks the function of epidermal growth factor receptor which is a key factor in
 stimulating liver cancer growth. In mice, gefitinib has been shown to reduce the size of
 liver cancer. It also had anti tumor activity in patients with various cancers including HCC.
 Gefitinib can relieve disease-related symptoms in these patients. Overall, gefitinib is a
 very well tolerated treatment and is suitable for long-term use.

 At the time of diagnosis and surgical evaluation, patients with resectable hepatocellular
 carcinoma will be asked to participate in this study.Patients will be registered after
 consent form is obtained. Patient is asked to donate tumor tissues, urine and blood
 samples.Tumor and normal specimens are collected at the time of surgery. After patient
 recovers from surgery (4-6 weeks) and fulfills the eligibility, patient will receive
 gefitinib 250 mg p.o. daily for 6 months.

 Patient will remain on study till completion of treatment. The following are conditions when
 your study doctor will remove you from the study or stop the therapy:

 1. Interruption of treatment for 4 consecutive weeks due to side effects, which do not
 resolve.

 2. withdraw of consent by patient. ii. Your disease becomes worse. iii. New information
 that gefitinib treatment is harmful to patients has become available.

 Patient will be evaluated at one month, 3 months and 6 months on gefitinib. After that,
 evaluate patient at least every 3 months for first 2 years, then every 6 months for next 3
 years, then yearly afterwards. Draw blood and store sera and urine at the same interval until
 relapse and/or death. Conduct correlative studies of urine, serum and tumor tissue with
 clinical outcome.
Inclusion Criteria:

 Pathologically newly diagnosis HCC, which is deemed resectable and resected.

 Patient has to start gefitinib within 6 weeks of hepatic resection with full recovery.

 Patients with positive resection margin or minimal residual disease (<0.5 cm) are also
 eligible.

 ECOG performance status (PS) 0, 1 or 2

 Patient must recover fully from hepatic resection ANC > 1,500/uL SGOT < 5 x UNL (upper
 normal limits) Plt > 75,000/uL Bilirubin < 2 x UNL Serum albumin ≥ 2.5g/dL

 Creatinine < 1.5 mg/dl or 125 u/L, alpha fetoprotein < 50 ug/L

 Signed informed consent

 Age > 18

 No space occupying lesion on CT scan of the liver i.e. normal CT scan post-resection. Small
 lesion in the liver after resection can be ablated by alcohol injection or radio frequency
 ablation and can make patient eligible.

 Negative pregnancy test of the blood within 7 days of starting treatment in female patient
 of childbearing potential.

 No prior systemic therapy or I131 or chemoembolization treatment after surgery.

 Can take or swallow medication orally i.e. no chronic or persistent nausea and vomiting

 No other malignancy except for adequately treated basal cell or squamous cell skin cancer
 or cervical cancer in-situ.

 No active infection, symptomatic CHF, unstable angina, uncontrolled cardiac arrhythmia and
 psychiatric disorder.

 No concomitant medications such as phenytoin, carbamazepine, rifampicin, barbiturates,
 ketoconazole and itraconazole, which are potent inducers of CYP3A4 or potent inhibitors of
 CYP3A4.

 Patient is not taking St. John's Wort.

 Exclusion Criteria:

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