A Phase II study of irinotecan in patients with advanced hepatocellular carcinoma

BACKGROUND. Advanced hepatocellular carcinoma has a poor prognosis. In a Ph ase II clinical trial, two academic centers assessed irinotecan, a topoisom erase-1 inhibitor with broad spectrum clinical activity, in patients who ha d advanced hepatocellular cancer. METHODS. Patients who had had up to one prior chemotherapy regimen were eli gible. Bidimensionally measurable disease, a good performance status, and a dequate major organ function were required. At a starting dose of 125 mg/m( 2), irinotecan was administered weekly for 4 weeks followed by a 2 week bre ak, which constituted 1 treatment cycle. Patients were restaged radiologica lly after two cycles of therapy. Dose attenuations were made as indicated f or toxicity. RESULTS. Fourteen patients were enrolled over a 10-week period in 1997. The re were ten males and four females. The median age was 58 years (range, 38- 74 yrs). The Eastern Cooperative Oncology Group median performance status w as 1 (range, 0-1). Two patients had prior chemotherapy (14%), and 1 patient (7%) had had radiation. A total of 30 cycles of therapy were delivered (me dian, 1; range, 1-6). Considerable toxicity was observed, mostly neutropeni a, diarrhea, nausea, vomiting, and fatigue. All patients required at least one dose attenuation for toxicity. One partial response (7%; confidence int erval, 0-20%) was noted to last 7 months. One patient had transient stable disease, and all others (86%) had progression of disease as their best resp onse. CONCLUSIONS. Irinotecan had modest activity in advanced hepatocellular canc er. Toxicity was substantial, presumably reflecting impaired underlying liv er function or poor ability to metabolize and eliminate the drug. The curre nt study indicated that continued new therapy assessment is warranted for t his disease. Cancer 2001; 91:101-5. (C) 2001 American Cancer Society.