| Literature DB >> 28988377 |
Phioanh Leia Nghiemphu1, Victoria Asuquo Ebiana2,3, Patrick Wen4, Mark Gilbert5, Lauren E Abrey6, F Lieberman7, Lisa M DeAngelis6, H Ian Robins8, W K Alfred Yung9, Susan Chang10, Jan Drappatz7, Minesh P Mehta11, Victor A Levin9, Kenneth Aldape12, Janet E Dancey13, J J Wright5, Michael Prados10, John Kuhn14, Timothy F Cloughesy2.
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.Entities:
Keywords: Combination study; Recurrent GBM; Sorafenib; Tipifarnib
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Year: 2017 PMID： 28988377 PMCID： PMC5756101 DOI： 10.1007/s11060-017-2624-4
Source DB: PubMed Journal: J Neurooncol ISSN： 0167-594X Impact factor: 4.130