title: Phase I study of vinflunine administered as a 10-minute infusion on days 1 and 8 every 3 weeks.
abstract: Vinflunine is a novel vinca alkaloid developed through the selective modification of vinorelbine using super-acidic chemistry. In preclinical testing, vinflunine demonstrated significantly enhanced anti-tumour activity in human tumour xenograft models when compared to its parent compound. A phase I study was conducted to evaluate the safety and toxicity of vinflunine administered as a 10 minute intravenous infusion on days 1 and 8 every three weeks. Sixteen patients with advanced solid tumours were treated. Two of four patients experienced dose limiting toxicities (DLT) at 190 mg/m2 and this was established as the maximum tolerated dose (MTD). At the MTD, the DLT of vinflunine consisted of constipation and neutropenia. Fatigue was notable but not dose limiting. No objective responses were observed. A dose of 170 mg/m2 given on a day 1 and 8 schedule every three weeks would be suitable for future studies.
authors.affiliation: Cancer Research UK Oncology Unit, Southampton University Hospitals, Southampton, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Johnson
authors.forename: Thomas
authors.initials: T
authors.lastname: Geldart
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Pinel
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
authors.forename: Ian
authors.initials: I
authors.lastname: Judson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D003248:Constipation / Q000139:chemically induced; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; C111217:vinflunine; D014747:Vinblastine