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

Abstract

BACKGROUND Advanced hepatocellular carcinoma has a poor prognosis. In a Phase II clinical trial, two academic centers assessed irinotecan, a topoisomerase‐1 inhibitor with broad spectrum clinical activity, in patients who had advanced hepatocellular cancer. METHODS Patients who had had up to one prior chemotherapy regimen were eligible. Bidimensionally measurable disease, a good performance status, and adequate major organ function were required. At a starting dose of 125 mg/m2, irinotecan was administered weekly for 4 weeks followed by a 2 week break, which constituted 1 treatment cycle. Patients were restaged radiologically after two cycles of therapy. Dose attenuations were made as indicated for toxicity. RESULTS Fourteen patients were enrolled over a 10‐week period in 1997. There were ten males and four females. The median age was 58 years (range, 38–74 yrs). The Eastern Cooperative Oncology Group median performance status was 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 (median, 1; range, 1–6). Considerable toxicity was observed, mostly neutropenia, diarrhea, nausea, vomiting, and fatigue. All patients required at least one dose attenuation for toxicity. One partial response (7%; confidence interval, 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 response. CONCLUSIONS Irinotecan had modest activity in advanced hepatocellular cancer. Toxicity was substantial, presumably reflecting impaired underlying liver function or poor ability to metabolize and eliminate the drug. The current study indicated that continued new therapy assessment is warranted for this disease. Cancer 2001;91:101–5. © 2001 American Cancer Society.

Prospective randomised phase II study of gemcitabine at standard or fixed dose rate schedule in unresectable hepatocellular carcinoma

“…Doxorubicin is widely considered the most active single-agent, but more recent studies have failed to demonstrate meaningful activity (Lai et al, 1988(Lai et al, , 1989Mok et al, 1999). Newer agents such as raltitrexed, paclitaxel, irinotecan, nolatrexed and eniluracil-5-fluorouracil have shown no activity (Rougier et al, 1997;Chao et al, 1998;Mok et al, 1999;Stuart et al, 1999;Llovet et al, 2001;O'Reilly et al, 2001). The present study did not show promising activity of singleagent gemcitabine.…”

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

“…Based on these characteristics of irinotecan, irinotecan was evaluated in phase II studies in patients with advanced HCC. Unfortunately, antitumor activity of single agent irinotecan was not significant with objective response rates of only 0-7% (20,21).…”

Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma

“…New chemotherapeutic drugs, such as paclitaxel, raltrexed, irinotecan, and nolatrexed, have not demonstrated encouraging results. These new drugs exhibit some antitumor activity, but response rates rarely exceed 10% (Rougier et al, 1997;Chao et al, 1998;O'Reilly et al, 1998;Stuart et al, 1999). The possible explanations for the refractioness of HCC to chemotherapy include tumor heterogeneity (Dexter and Leith, 1986), inadequate dosage of anticancer agents (Lai et al, 1990) and the inducible overexpression of the multidrug resistance gene (Huang et al, 1992).…”