Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Role of TPMT and ITPA variants in mercaptopurine disposition

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Withdrawal: Identification of tumor antigens among the HLA peptidomes of glioblastoma tumors and plasma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Actively personalized vaccination trial for newly diagnosed glioblastoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Extracranial metastases in glioblastoma-Two case stories

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Vincent A de Weger
  • Sanjay Goel
  • Roger von Moos
  • Jan H M Schellens
  • Nicholas Mach
  • Eugene Tan
  • Suraj Anand
  • Jeffrey W Scott
  • Ulrik Lassen
View graph of relations

PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors.

METHODS: Non-smoking patients of ≥ 18 years with advanced solid tumors, excluding breast cancer, were included. Patients were treated with a dose of 300 mg in 5 days on/2 days off schedule. Steady-state pharmacokinetic assessments of dovitinib were performed with or without fluvoxamine.

RESULTS: Forty-five patients were enrolled; 24 were evaluable for drug-drug interaction assessment. Median age was 60 years (range 30-85). At steady state the geometric mean for dovitinib (coefficient of variation%) of the area under the plasma concentration-time curve (AUC0-72h) and maximum concentration (C max) were 2880 ng/mL h (47%) and 144 ng/mL (41%), respectively. Following administration of dovitinib in combination with fluvoxamine the geometric mean of dovitinib AUC0-72h and C max were 8290 ng/mL h (60%) and 259 ng/mL (45%), respectively. The estimated geometric mean ratios for dovitinib AUC0-72h and C max (dovitinib + fluvoxamine vs. dovitinib alone) were 2.88 [90% confidence interval (CI) 2.58, 3.20] and 1.80 (90% CI 1.66, 1.95). This effect is considered a moderate drug-drug interaction.

CONCLUSIONS: Fluvoxamine co-administration resulted in a 80% increase in C max and a 188% increase in AUC0-72h of dovitinib. Given the increase in exposure to dovitinib observed, patients are at risk of dovitinib related toxicity. Dovitinib should, therefore, not be co-administered with moderate and strong CYP1A2 inhibitors, without dose reduction.

Original languageEnglish
JournalCancer Chemotherapy and Pharmacology
Volume81
Issue number1
Pages (from-to)73-80
ISSN0344-5704
DOIs
Publication statusPublished - 2018

    Research areas

  • Journal Article

ID: 52045343