Phase II study to topotecan and cisplatin in advanced hepatocellular carcinoma

Hepatocellular carcinoma remains a highly chemoresistant neoplasm and is a common malignancy with poor prognosis in Korea. We performed a phase II study to evaluate the efficacy and toxicities of topotecan and cisplatin combination chemotherapy for advanced hepatocellular carcinoma. Between November 1999 and May 2001, ten patients with histologically proven hepatocellular carcinoma were enrolled in this study. The median age was 54 (range: 53-74) years and all were male. Six patients demonstrated stage IV, 1 stage IIIC, 2 stage IIIB and 1 stage IIIA. Six patients showed a ECOG performance status of 1. The treatment regimen consisted of topotecan 1.25 mg/m2 and cisplatin 20 mg/m2 for 5 days. The treatment was repeated every 4 weeks. Toxicities were evaluated according to WHO toxicity criteria. All ten patients were evaluable for response and toxicity. There was only one patient who achieved partial response. The overall response rate was 10% (95% C.I.) and the response duration was 46 weeks. The median survival of all patients was 21 (range: 17-54+) weeks. During a total of 24 cycles, neutropenia of WHO grade 3 and 4 occurred in 33%, thrombocytopenia in 33% and anemia in 21%. In non-hematologic toxicity, diarrhea and hepatoxicity of grade 3 occurred in 1 and 2 patients, respectively. But there was no treatment-related death. When used in this dose and schedule, topotecan and cisplatin combination chemotherapy does not seem to be effective for patients with advanced hepatocellular carcinoma.