Based upon the radiation sensitization properties of the halogenated
pyrimidines,
5-iododeoxyuridine (IdUrd) and
5-bromodeoxyuridine, long term i.v. infusions of halogenated
pyrimidines in conjunction with fractionated
radiation therapy have been evaluated in the treatment of a variety of human
malignancies. While clinical studies have attempted to measure the halogenated
pyrimidine incorporation, few have successfully related
tumor response to the incorporation of IdUrd by the
tumor. The present study reports the continuous IdUrd labeling index (number of cells labeled) and the IdUrd corrected replacement (percentage of
thymidine replacement in the labeled cells of the population) from the
tumors of 17 patients who received continuous infusions of IdUrd (1000 mg/m2/24 h). The
tumors treated included four high grade
gliomas, five head and neck
tumors, four high grade
sarcomas, and five other
tumors of varying types. Less than 25% of the cells in three of four
gliomas incorporated IdUrd after 5-7-day IdUrd infusion time. Corrected replacement for the
gliomas ranged from 0 to 4%. In contrast, 63-85% of the cells in the head and neck biopsies were labeled with IdUrd after 3-7-day IdUrd infusions suggesting that these large
tumors (3-12 cm diameter) have a high fraction of dividing cells. Corrected replacements values for the head and neck
tumor patients ranged from 2.9 to 26.3%. The high grade
sarcomas also demonstrated a high percentage of IdUrd labeled cells (57-79%) with three patients having corrected replacements of 7.5-14.2%. The continuous labeling and
thymidine replacement data for four patients from whom serial biopsies were taken during IdUrd infusion demonstrated both an increasing IdUrd replacement and continuous labeling index with an increasing duration of IdUrd infusion. The clinical response of both the high grade
glioma and head and neck
tumor patients indicate that the IdUrd replacement and labeling data may provide some important predictive information with regard to the successful use of the halogenated
pyrimidines in clinical radiation trials.