TY - JOUR
T1 - A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07)
AU - Hutterer, Markus
AU - Nowosielski, Martha
AU - Haybaeck, Johannes
AU - Embacher, Sabine
AU - Stockhammer, Florian
AU - Gotwald, Thaddäus
AU - Holzner, Bernhard
AU - Capper, David
AU - Preusser, Matthias
AU - Marosi, Christine
AU - Oberndorfer, Stefan
AU - Moik, Martin
AU - Buchroithner, Johanna
AU - Seiz, Marcel
AU - Tuettenberg, Jochen
AU - Herrlinger, Ulrich
AU - Wick, Antje
AU - Vajkoczy, Peter
AU - Stockhammer, Günther
PY - 2014/1
Y1 - 2014/1
N2 - BACKGROUND: Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing.METHODS: This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules.RESULTS: Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5%, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed prolonged stable disease ≥6 months with a median PFS of 16.0 months (range, 6.4-41.4 mo) and a median OS of 46.9 months (range, 21.2-49.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n = 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated treatment due to toxicity.CONCLUSION: Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS. ClinicalTrials.gov Identifier: NCT00535379.
AB - BACKGROUND: Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing.METHODS: This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules.RESULTS: Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5%, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed prolonged stable disease ≥6 months with a median PFS of 16.0 months (range, 6.4-41.4 mo) and a median OS of 46.9 months (range, 21.2-49.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n = 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated treatment due to toxicity.CONCLUSION: Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS. ClinicalTrials.gov Identifier: NCT00535379.
KW - Adult
KW - Aged
KW - Angiogenesis Inhibitors/therapeutic use
KW - Brain Neoplasms/drug therapy
KW - Drug Administration Schedule
KW - Female
KW - Follow-Up Studies
KW - Glioblastoma/drug therapy
KW - Humans
KW - Indoles/therapeutic use
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local/drug therapy
KW - Neoplasm Staging
KW - Prognosis
KW - Prospective Studies
KW - Pyrroles/therapeutic use
KW - Sunitinib
KW - Survival Rate
UR - http://www.scopus.com/inward/record.url?scp=84891527003&partnerID=8YFLogxK
U2 - 10.1093/neuonc/not161
DO - 10.1093/neuonc/not161
M3 - Journal article
C2 - 24311637
SN - 1522-8517
VL - 16
SP - 92
EP - 102
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 1
ER -