title: A phase 1/2 study of orally administered synthetic hypericin for treatment of recurrent malignant gliomas.
abstract: BACKGROUND
  Hypericin is a potent inhibitor of glioma growth in vitro. To examine whether synthetic oral hypericin can be tolerated by patients with recurrent malignant gliomas (anaplastic astrocytoma and glioblastoma) and to investigate its efficacy against these tumors, the authors undertook an open-label, sequential dose escalation/de-escalation tolerance study.
  
  
  METHODS
  Patients with documented recurrent or progressive malignant gliomas who had received standard radiation therapy with or without chemotherapy were included. Patients were excluded for previous treatment with agents known to contain hypericin or treatment within 30 days with medications known to cause photosensitivity. Enrolled patients were given gradually increasing dosages of oral synthetic hypericin (0.05-0.50 mg/kg) for up to 3 months if no toxicity was observed, and patient response to treatment was noted. The patients were examined each month and underwent magnetic resonance imaging to evaluate tumor status at 3 months.
  
  
  RESULTS
  Synthetic hypericin administered orally appeared to provide stabilization or a slight (<50%) decrease in tumor volume (coded as stable disease) at 3 months for 7 of 42 patients (17%) and produced a tumor reduction >50% (partial response) in 2 patients (5%). Seventeen patients (40%) survived for 3 months on daily synthetic hypericin at dose levels of 0.33 ± 0.070 mg/kg daily. The mean maximum tolerated dose was 0.40 ± 0.098 mg/kg daily. Twelve patients continued on hypericin therapy beyond 3 months. The median survival was 26 weeks (Kaplan-Meier method).
  
  
  CONCLUSIONS
  The results of this study indicated that synthetic, oral hypericin is well tolerated in this patient group. The response results were comparable to those reported from other studies of salvage therapies for recurrent malignant brain tumors.
authors: Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84132, USA. neuropub@hsc.utah.edu
authors: William T
authors: WT
authors: Couldwell
authors: Amy A
authors: AA
authors: Surnock
authors: Alfonso J
authors: AJ
authors: Tobia
authors: Bernard E
authors: BE
authors: Cabana
authors: Charles B
authors: CB
authors: Stillerman
authors: Peter A
authors: PA
authors: Forsyth
authors: Alan J
authors: AJ
authors: Appley
authors: Alexander M
authors: AM
authors: Spence
authors: David R
authors: DR
authors: Hinton
authors: Thomas C
authors: TC
authors: Chen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy; D005260:Female; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D010569:Perylene; C004965:hypericin