Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas

Background/Aims: Patients with advanced unresectable hepatobiliary carcinom as have a dismal prognosis. The efficacy of systemic chemotherapy in these patients is negligible and often, in particular in patients with hepatocell ular carcinomas, the toxicity of chemotherapy outweighs the potential palli ative effect of antineoplastic agents. Gemcitabine is a new anticancer agen t with a mild toxicity profile, which has demonstrated antineoplastic activ ity in many solid tumors. Therefore we investigated the effect of gemcitabi ne in patients with advanced nonresectable hepatocellular and cholangiocell ular carcinomas in a phase II study. Methododology: Twenty-three patients with cholangiocellular carcinoma and 2 0 patients with hepatocellular carcinoma were enrolled into the study. Eigh teen of the 20 patients with hepatocellular carcinomas had Liver cirrhosis. Gemcitabine was administered once weekly over 30min for 3 consecutive week s out of every 4 weeks. Patients with cholangiocellular carcinomas received gemcitabine also in the forth week of the first cycle with no rest to the following cycle. Disease status was assessed every 4 weeks. Results: Overall the regimen was well tolerated. The median number of gemci tabine administration a was 15 (range, 3-37) in the group of patients with cholangiocellular carcinomas and 7.6 (range, 3-21) in the group of patients with hepatocellular carcinomas. In the group of patients with hepatocellul ar carcinomas thrombocytopenia was the most frequent side effect (30% grade 3/4). Among the patients with cholangiocellular carcinomas nausea and neut ropenia were the most commonly observed side effects. The overall response rate of hepatocellular carcinomas was only 5% and chemotherapy generally di d not improve the tumor symptoms of the patients in this group. In contrast , in the group of cholangiocellular carcinomas, seven patients achieved a p artial response (overall response rate 30%). Eleven patients with cholangio cellular carcinomas revealed tumor symptoms before the onset of gemcitabine treatment. Seven of these patients developed a treatment related clinical benefit as defined as a relief of tumor symptoms or gain of weight. Conclusions: Our results indicate that the treatment of cholangiocarcinomas with gemcitabine is effective and should be further evaluated in phase III studies. In contrast,.palliative chemotherapy with gemcitabine cannot be r ecommended in patients with hepatocellular carcinoma and Liver cirrhosis.