Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02 Journal Article

   


Authors: Nghiemphu, P. L.; Ebiana, V. A.; Wen, P.; Gilbert, M.; Abrey, L. E.; Lieberman, F.; DeAngelis, L. M.; Robins, H. I.; Yung, W. K. A.; Chang, S. S.; Drappatz, J.; Mehta, M. P.; Levin, V. A.; Aldape, K.; Dancey, J. E.; Wright, J. J.; Prados, M.; Kuhn, J.; Cloughesy, T. F.
Article Title: Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02
Abstract: Recurrent glioblastoma (GBM) has a very low 6-month progression free survival (PFS) with currently available treatments. Combination chemotherapy to target multiple cell signaling pathways is currently being investigated in order to improve prognosis for recurrent disease. The purpose of this phase I study was to determine the maximum tolerated dose (MTD) for the combination of tipifarnib and sorafenib for the treatment of recurrent GBM. Patients with pathologically proven WHO grade IV GBM and radiographically proven tumor recurrence were eligible for this study. Treatments included sorafenib at twice daily and escalating dosages of tipifarnib. Dose-limiting toxicity (DLT) was determined over the first 28-days of treatments, and the MTD was determined in a 3 + 3 study design. We enrolled 24 patients, and 21 patients completed the MTD period. The study was stopped early with no MTD determination for excessive toxicities. The last dose level reached was sorafenib at 200 mg twice a day and tipifarnib 100 mg twice a day on an alternating week schedule. The DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia. The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination. © 2017, Springer Science+Business Media, LLC.
Keywords: sorafenib; tipifarnib; recurrent gbm; combination study
Journal Title: Journal of Neuro-Oncology
Volume: 136
Issue: 1
ISSN: 0167-594X
Publisher: Springer  
Date Published: 2018-01-01
Start Page: 79
End Page: 86
Language: English
DOI: 10.1007/s11060-017-2624-4
PROVIDER: scopus
PMCID: PMC5756101
PUBMED: 28988377
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030714995&doi=10.1007%2fs11060-017-2624-4&partnerID=40&md5=6771389a7e72c57c1c0cc28c02da24fd
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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MSK Authors
  1. Lisa De Angelis
    576 De Angelis
  2. Lauren E Abrey
    278 Abrey
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