title: Irinotecan as first-line chemotherapy in patients with advanced hepatocellular carcinoma: a multicenter phase II study with dose adjustment according to baseline serum bilirubin level.
abstract: This study assessed the clinical activity and safety of irinotecan (CPT-11) in patients with advanced hepatocellular carcinoma (HCC) using dose adjustment according to baseline serum bilirubin level. Patients with advanced HCC received CPT-11 at a dose of 350 mg/m(2) when total bilirubin level was 1.5 times upper limit of normal (ULN) (group A), or 200 mg/m(2) when total bilirubin level was between 1.51 and 3 ULN (group B). No objective response, one minor response and 12 disease stabilizations were observed in the 29 patients (group A, 23; group B, 6) enrolled. Median time to progression and overall survival were 3.1 months (95% confidence interval [CI]: 2.0-4.0) and 7.4 months (95% CI: 3.9-12.0), respectively. Grade 3-4 adverse events (mostly neutropenia [47%], anaemia [24%], and diarrhoea [17%]) were more frequent in group A (74%) than in group B (33%) (P = 0.086). This study found favourable toxicity profile using dosage adjustment to the baseline total bilirubin level in patients with bilirubin level comprised between 1.51 and 3 ULN. However, the antitumour activity of single agent CPT-11 was not significant in advanced HCC.
authors.affiliation: Gastrointestinal Oncology Unit, Department of Medicine, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. boige@igr.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Boige
authors.forename: Julien
authors.initials: J
authors.lastname: Taïeb
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hebbar
authors.forename: David
authors.initials: D
authors.lastname: Malka
authors.forename: Thierry
authors.initials: T
authors.lastname: Debaere
authors.forename: Laurent
authors.initials: L
authors.lastname: Hannoun
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Magherini
authors.forename: Dominique
authors.initials: D
authors.lastname: Mignard
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
mesh_terms: D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D000077146:Irinotecan; D001663:Bilirubin; D002166:Camptothecin