title: Measurement of thymidine replacement in patients with high grade gliomas, head and neck tumors, and high grade sarcomas after continuous intravenous infusions of 5-iododeoxyuridine.
abstract: 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.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
authors.forename: J A
authors.initials: JA
authors.lastname: Cook
authors.forename: J
authors.initials: J
authors.lastname: Glass
authors.forename: R
authors.initials: R
authors.lastname: Lebovics
authors.forename: H
authors.initials: H
authors.lastname: Bobo
authors.forename: H
authors.initials: H
authors.lastname: Pass
authors.forename: T F
authors.initials: TF
authors.lastname: DeLaney
authors.forename: E H
authors.initials: EH
authors.lastname: Oldfield
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: E
authors.initials: E
authors.lastname: Glatstein
authors.forename: T E
authors.initials: TE
authors.lastname: Goffman
mesh_terms: D000818:Animals; D002460:Cell Line; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D051379:Mice; D008809:Mice, Inbred C3H; D008940:Mitotic Index; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D013936:Thymidine / Q000032:analysis*; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D007065:Idoxuridine; D013936:Thymidine