title: Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma.
abstract: The majority of patients with hepatocellular carcinoma will develop either unresectable or metastatic disease and, therefore, are candidates for systemic chemotherapy. Only a few chemotherapeutic agents have shown documented activity in the treatment of advanced hepatocellular carcinoma and there is clearly a need for the evaluation of new active drugs. Therefore, we performed a phase I trial with a weekly schedule of paclitaxel in patients with advanced hepatocellular carcinoma. 16 patients with documented progression of unresectable hepatocellular carcinoma were included. After premedication, paclitaxel was given as a 1 h infusion on days 1, 8, 15, 22, 29 and 36 representing one treatment cycle. The cycle was repeated every 50 days. The starting dose was 70 mg/m2 and the doses were escalated in steps of 10 mg/m2/week. A minimum of 3 patients were treated at each dose level. All treatment was given on an out-patient basis. Dose-limiting toxicity was reached at a dose of 100 mg/m2/week with 2 of 6 patients treated at that dose level having WHO grade 4 neutropenia. Other toxic side-effects were only mild. 1 partial response and 9 cases with disease stabilisation were observed in 16 patients with initially progressive disease. We, therefore, conclude that the recommended dose for a further phase II trial in patients with hepatocellular carcinoma is 90 mg/m2/week. These data indicate that paclitaxel given at this dose and schedule might have activity in hepatocellular carcinoma and further investigation in phase II trials is warranted.
authors.affiliation: Department of Internal Medicine (Cancer Research), West German Cancer Centre, Essen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Strumberg
authors.forename: J
authors.initials: J
authors.lastname: Erhard
authors.forename: A
authors.initials: A
authors.lastname: Harstrick
authors.forename: U
authors.initials: U
authors.lastname: Klaassen
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: W
authors.initials: W
authors.lastname: Eberhardt
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.forename: S
authors.initials: S
authors.lastname: Seeber
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel