title: A pilot study of hypofractionated stereotactic radiation therapy and sunitinib in previously irradiated patients with recurrent high-grade glioma.
abstract: OBJECTIVE
  Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG).
  
  
  METHODS
  Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging.
  
  
  RESULTS
  Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%.
  
  
  CONCLUSIONS
  Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: evan.wuthrick@osumc.edu.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Wuthrick
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
authors.affiliation: Department of Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lin
authors.affiliation: Department of Neurological Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Jon
authors.initials: J
authors.lastname: Glass
authors.affiliation: Department of Neurological Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: James
authors.initials: J
authors.lastname: Evans
authors.affiliation: Department of Neurological Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
authors.affiliation: Department of Medical Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Rita
authors.initials: R
authors.lastname: Axelrod
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Wenyin
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.affiliation: Department of Radiology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan; Department of Biomedical Engineering, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: E Mark
authors.initials: EM
authors.lastname: Haacke
authors.affiliation: Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Gilda G
authors.initials: GG
authors.lastname: Hillman
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D016634:Radiosurgery / Q000379:methods*; D012074:Remission Induction; D019233:Retreatment / Q000379:methods; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
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