title: Results of the phase I dose-escalating study of motexafin gadolinium with standard radiotherapy in patients with glioblastoma multiforme.
abstract: OBJECTIVE
  Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme.
  
  
  METHODS
  A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied.
  
  
  RESULTS
  The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94).
  
  
  CONCLUSIONS
  The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095-6951, USA. judithathome@earthlink.net
authors.forename: Judith M
authors.initials: JM
authors.lastname: Ford
authors.forename: Wendy
authors.initials: W
authors.lastname: Seiferheld
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Alger
authors.forename: Genevieve
authors.initials: G
authors.lastname: Wu
authors.forename: Thyra J
authors.initials: TJ
authors.lastname: Endicott
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
authors.forename: Walter
authors.initials: W
authors.lastname: Curran
authors.forename: See-Chun
authors.initials: SC
authors.lastname: Phan
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016555:Matched-Pair Analysis; D020714:Maximum Tolerated Dose; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium