Format

Send to

Choose Destination
J Cancer Res Clin Oncol. 2016 Jul;142(7):1581-9. doi: 10.1007/s00432-016-2161-0. Epub 2016 Apr 21.

Phase I trial of dovitinib (TKI258) in recurrent glioblastoma.

Author information

1
Division of Clinical Neurooncology, Department of Neurology, Medical Center Bonn, 53127, Bonn, Germany.
2
Stem Cell Pathologies, Institute of Reconstructive Neurobiology, University of Bonn, 53127, Bonn, Germany.
3
Institute of Neuropathology, Medical Center Bonn, 53127, Bonn, Germany.
4
Institute of Bioinformatics, Medical Center Bonn, 53127, Bonn, Germany.
5
Department of Neurosurgery, Medical Center Bonn, 53127, Bonn, Germany.
6
Study Center Bonn, Institute of Clinical Chemistry and Clinical Pharmacology, Medical Center Bonn, 53127, Bonn, Germany.
7
Division of Translational Oncology/Neurooncology, German Cancer Research Center (DKFZ), Heidelberg; West German Cancer Center (WTZ) and German Cancer Consortium (DKTK), University Hospital Essen, 45147, Essen, Germany.
8
Division of Clinical Neurooncology, Department of Neurology, Medical Center Bonn, 53127, Bonn, Germany. Martin.Glas@ukb.uni-bonn.de.
9
Stem Cell Pathologies, Institute of Reconstructive Neurobiology, University of Bonn, 53127, Bonn, Germany. Martin.Glas@ukb.uni-bonn.de.
10
Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik, 53129, Bonn, Germany. Martin.Glas@ukb.uni-bonn.de.

Abstract

PURPOSE:

Dovitinib (TKI258) is an oral multi-tyrosine kinase inhibitor of FGFR, VEGFR, PDGFR β, and c-Kit. Since dovitinib is able to cross the blood-brain barrier and targets brain tumor-relevant pathways, we conducted a phase I trial to demonstrate its safety in recurrent glioblastoma (GBM).

PATIENTS AND METHODS:

Patients with first or second GBM recurrence started treatment with the maximal tolerated dose (MTD) previously established in systemic cancer patients (500 mg/d, 5 days on/2 days off). A modified 3 + 3 design in three cohorts (500, 400, 300 mg) was used.

RESULTS:

Twelve patients were enrolled. Seventy-two adverse events (AEs) occurred and 16.7 % of AEs were classified as ≥CTC grade 3 toxicity, mainly including hepatotoxicity and hematotoxicity. Only one out of six patients of the 300-mg cohort showed grade 3 toxicity. The PFS-6 rate was 16.7 %, and it was not associated with detection of the FGFR-TACC gene fusion in the tumor.

CONCLUSION:

Dovitinib is safe in patients with recurrent GBM and showed efficacy in only some patients unselected for target expression. The recommended phase II dose of 300 mg would be substantially lower than the recently established MTD in systemic cancer patients. Further personalized trials are recommended.

KEYWORDS:

Dovitinib; FGFR; Phase I trial; Recurrent glioblastoma; TKI258; Tyrosine kinase inhibitor

PMID:
27100354
DOI:
10.1007/s00432-016-2161-0
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center