title: A phase I clinical and pharmacokinetic study evaluating vinflunine in combination with epirubicin as first-line treatment in metastatic breast cancer.
abstract: BACKGROUND
  Vinflunine (VFL) is a bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with epirubicin (EPR) to establish the recommended dose (RD), to evaluate the safety and efficacy profiles and to investigate potential pharmacokinetic (PK) drug-drug interaction (DDI).
  
  
  METHODS
  Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first-line chemotherapy of metastatic breast cancer patient. PK DDI was evaluated through population PK approaches.
  
  
  RESULTS
  Thirty-nine patients received a total of 197 cycles of the VFL-EPR combination (median 6). The RDs were VFL 250 mg/m(2) + EPR 75 mg/m(2) every 3 weeks for schedule 1 and VFL 170 mg/m(2) + EPR 35 mg/m(2) every 3 weeks for schedule 2. The PK analysis demonstrated no clinically relevant mutual DDI between VFL and EPR. The main dose-limiting toxicity was neutropenia. The most frequent non-haematological adverse events were nausea, fatigue, constipation, vomiting, anorexia and stomatitis. Objective response rate was achieved in 45.9 % of the patients.
  
  
  CONCLUSIONS
  VFL-EPR combination is feasible with manageable toxicity. The antitumour activity was promising and supports further evaluation.
authors.affiliation: Nottingham City Hospital, Nottingham, UK, steve.chan@nuh.nhs.uk.
authors.forename: S
authors.initials: S
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
authors.forename: M
authors.initials: M
authors.lastname: Bostnavaron
authors.forename: L
authors.initials: L
authors.lastname: Nguyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015251:Epirubicin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D015251:Epirubicin; C111217:vinflunine; D014747:Vinblastine