Salvage therapy for hepatocellular carcinoma with thalidomide

To evaluate the clinical benefit of thalidomide in patients with advanced hepatocellular carcinoma (hepatoma).

From March 2000 to July 2002, patients who had advanced hepatocellular carcinoma and failed to or were unsuited for aggressive treatment, were enrolled and took thalidomide 150 to 300 mg/d. All cases were followed till April 2003. Data collection included viral hepatitis, grade of cirrhosis, total dosage of thalidomide, side effect, stage of hepatoma by Okuda and CLIP classification, and prognosis. The subjects were divided into A and B groups, depending on 5 000 mg dosage of thalidomide. Survival time of all cases and in the two subgroups was evaluated.

Ninety-nine patients with hepatoma were enrolled, 81 men and 18 females with median age 58+/-14.1 years. Eighty-six percent had viral hepatitis and one case was alcoholism. Hepatoma was diagnosed with histology, alpha-fetoprotein (aFP) >400 ng/mL, or image examination, there were 30, 33 and 36 cases respectively. At the time of thalidomide therapy, more than 81% had cirrhotic status. Twenty-two patients were in group A (< 5 000 mg) with median survival time about 25 days, for 77 cases in group B (> =5 000 mg) the median survival time was about 109 days. Six subjects had partial response. Most adverse effects were skin rush, neuropathy, somnolence, and constipation.

Several patients responded to thalidomide therapy. As a single drug therapy, thalidomide might not have good therapeutic effect for all cases, but a small ratio of patients had exciting response, the resistance or tumor escape would develop after long-term use. Up to now, no defined facts could be used to predict response. The effect of thalidomide on hepatoma might be associated with the dosage. As salvage therapy, thalidomide has its value. Combination or adjuvant therapy will be the next trial.