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Journal of Cancer Research and Clinical Oncology

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01-07-2016 | Original Article – Clinical Oncology

Phase I trial of dovitinib (TKI258) in recurrent glioblastoma

Authors: Niklas Schäfer, Gerrit H. Gielen, Sied Kebir, Anja Wieland, Andreas Till, Frederic Mack, Christina Schaub, Theophilos Tzaridis, Roman Reinartz, Michael Niessen, Rolf Fimmers, Matthias Simon, Christoph Coch, Christine Fuhrmann, Ulrich Herrlinger, Björn Scheffler, Martin Glas

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2016

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.

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Title: Phase I trial of dovitinib (TKI258) in recurrent glioblastoma
Authors: Niklas Schäfer
Gerrit H. Gielen
Sied Kebir
Anja Wieland
Andreas Till
Frederic Mack
Christina Schaub
Theophilos Tzaridis
Roman Reinartz
Michael Niessen
Rolf Fimmers
Matthias Simon
Christoph Coch
Christine Fuhrmann
Ulrich Herrlinger
Björn Scheffler
Martin Glas
Publication date: 01-07-2016
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 7/2016
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2161-0

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