title: Long-term follow-up on National Cancer Institute Phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation.
abstract: OBJECTIVE
  We report the results of the final phase I/II program in glioblastoma (GBM) multiforme patients using only hyperfractionated irradiation and intravenous iododeoxyuridine (IdUrd).
  
  
  METHODS
  For a decade we investigated halogenated pyrimidine radiosensitizers in an effort to exploit the potential for differential uptake of thymidine analogs between proliferating tumor and normal brain tissues. Trials began with bromodeoxyuridine (BrdUrd) but were changed to IdUrd when the latter proved less photosensitizing. A series of dose-escalating pilot trials led to treatment at a maximum-tolerated dose (MTD) of IdUrd of 1,000 mg/m2/d for two separate 14-day courses, one during the initial radiation field and one during the cone down. The radiotherapy also evolved over time and was hyperfractionated in all cases reported. Over 5 years we accrued 45 patients into the final hyperfractionated, 1,000 mg/m2/d scheme. We report here results on only the patients with minimum follow-up of 1 year (90% had at least 2 years of follow-up) or until death.
  
  
  RESULTS
  The results do not indicate a significant benefit for use of sensitizers, as compared with other contemporary and aggressive types of radiation treatment. The median survival has been 11 months, with a 2-year actuarial survival of 9%. As yet, there are no survivors at 3 years. Tumor biopsies at craniotomy showed relatively low sensitizer incorporation.
  
  
  CONCLUSIONS
  The failure of radiosensitizers combined with radiation therapy to show major benefit may be due to patient selection but appears also to be related to the combined problems of poor drug penetration/uptake into tumor, tumor-cell heterogeneity, and a high inherent cellular radioresistance of GBM.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892.
authors.forename: T E
authors.initials: TE
authors.lastname: Goffman
authors.forename: L J
authors.initials: LJ
authors.lastname: Dachowski
authors.forename: H
authors.initials: H
authors.lastname: Bobo
authors.forename: E H
authors.initials: EH
authors.lastname: Oldfield
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: J
authors.initials: J
authors.lastname: Cook
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: D
authors.initials: D
authors.lastname: Katz
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Glatstein
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000532:radiotherapy*; D004341:Drug Evaluation; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D007065:Idoxuridine / Q000627:therapeutic use*; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D016019:Survival Analysis
chemical_list: D011838:Radiation-Sensitizing Agents; D007065:Idoxuridine