title: A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers.
abstract: The prognosis of advanced biliary tract carcinoma is poor with chemotherapy limited to a palliative role. This randomised study was designed to evaluate the effectiveness of a new liposomal thymidylate synthase inhibitor (TSI), OSI-7904L, in parallel with a modified de Gramont regimen of 5-FU/LV in patients with advanced biliary cancer. Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI-7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5-FU/LV (intravenous l-LV 200 mg/m2, bolus 5-FU 400 mg/m2 and a 46-h infusion of 5-FU 2,400 mg/m2) every 14 days. Twenty-two patients were randomised, 11 to each group. No patients responded in the OSI-7904L arm, while one patient achieved a partial response in the 5-FU/LV arm. The rates of disease stabilisation were 4/11 (OSI-7904L) and 10/11 (5-FU/LV). Both treatment arms were generally well tolerated. These results show that the activity of OSI-7904L is below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilisation. A simplified de Gramont schedule appears to have marginally more activity. Both treatments were well tolerated.
authors.affiliation: Oncology Institute Ion Chiricuta, 34-36 Gh. Bilascu Street, 3400, Cluj-Napoca, Romania. tudor@iocn.ro
authors.forename: T
authors.initials: T
authors.lastname: Ciuleanu
authors.forename: M
authors.initials: M
authors.lastname: Diculescu
authors.forename: N M
authors.initials: NM
authors.lastname: Hoepffner
authors.forename: J
authors.initials: J
authors.lastname: Trojan
authors.forename: V
authors.initials: V
authors.lastname: Sailer
authors.forename: M
authors.initials: M
authors.lastname: Zalupski
authors.forename: T
authors.initials: T
authors.lastname: Herrmann
authors.forename: A
authors.initials: A
authors.lastname: Roth
authors.forename: J
authors.initials: J
authors.lastname: Chick
authors.forename: K
authors.initials: K
authors.lastname: Brock
authors.forename: D
authors.initials: D
authors.lastname: Albert
authors.forename: P A
authors.initials: PA
authors.lastname: Philip
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005977:Glutarates / Q000627:therapeutic use*; D006801:Humans; D054833:Isoindoles; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: C506644:((S)-2-(5-(1,2-dihydro-3-methyl-1-oxobenzo(f)-quinazoline-9-yl)methyl)amino-1-oxo-2-isoindolynyl)-glutaric acid; D000970:Antineoplastic Agents; D005977:Glutarates; D054833:Isoindoles; D011799:Quinazolines; D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil