title: A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07).
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Corresponding author: Markus Hutterer, MD, Department of Neurology and Wilhelm-Sander NeuroOncology Unit, University of Regensburg Medical School, Franz Josef Strauß-Allee 11, D-93053 Regensburg, Germany. markus.hutterer@ukr.de.
authors: Markus
authors: M
authors: Hutterer
authors: Martha
authors: M
authors: Nowosielski
authors: Johannes
authors: J
authors: Haybaeck
authors: Sabine
authors: S
authors: Embacher
authors: Florian
authors: F
authors: Stockhammer
authors: Thaddäus
authors: T
authors: Gotwald
authors: Bernhard
authors: B
authors: Holzner
authors: David
authors: D
authors: Capper
authors: Matthias
authors: M
authors: Preusser
authors: Christine
authors: C
authors: Marosi
authors: Stefan
authors: S
authors: Oberndorfer
authors: Martin
authors: M
authors: Moik
authors: Johanna
authors: J
authors: Buchroithner
authors: Marcel
authors: M
authors: Seiz
authors: Jochen
authors: J
authors: Tuettenberg
authors: Ulrich
authors: U
authors: Herrlinger
authors: Antje
authors: A
authors: Wick
authors: Peter
authors: P
authors: Vajkoczy
authors: Günther
authors: G
authors: Stockhammer
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: antitumor activity and safety; glioblastoma; molecular markers; quality of life; sunitinib