Journal of Clinical Oncology, Vol 10, 264-268, Copyright © 1992 by American Society of Clinical Oncology
Long-term follow-up on National Cancer Institute Phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation
TE Goffman, LJ Dachowski, H Bobo, EH Oldfield, SM Steinberg, J Cook, JB Mitchell, D Katz, R Smith and E Glatstein
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892.
PURPOSE: 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. CONCLUSION: 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.
