A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07)

Markus Hutterer, Martha Nowosielski, Johannes Haybaeck, Sabine Embacher, Florian Stockhammer, Thaddäus Gotwald, Bernhard Holzner, David Capper, Matthias Preusser, Christine Marosi, Stefan Oberndorfer, Martin Moik, Johanna Buchroithner, Marcel Seiz, Jochen Tuettenberg, Ulrich Herrlinger, Antje Wick, Peter Vajkoczy, Günther Stockhammer

Research output: Journal article (peer-reviewed)Journal article

50 Citations (Scopus)

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.

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.

Original languageEnglish
Pages (from-to)92-102
Number of pages11
JournalNeuro-Oncology
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Adult
  • Aged
  • Angiogenesis Inhibitors/therapeutic use
  • Brain Neoplasms/drug therapy
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Glioblastoma/drug therapy
  • Humans
  • Indoles/therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local/drug therapy
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Pyrroles/therapeutic use
  • Sunitinib
  • Survival Rate

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