Iododeoxyuridine (IdUrd) incorporation into DNA of human hematopoietic cells, normal liver and hepatic metastases in man: as a radiosensitizer and as a marker for cell kinetic studies.
Iododeoxyuridine (IdUrd) was administered as a continuous infusion for 14 days to patients with glioblastoma and sarcoma, and for 3 days to patients with metastatic colorectal carcinoma. In the first group, the maximum incorporation of IdUrd into DNA was determined, taking granulocytes as parameter. In the second group, selective incorporation into DNA of normal liver and hepatic metastases of colorectal cancer was investigated. The highest dose of 675 mg/sq.m./day for 14 days produced IdUrd plasma concentrations of 1.8 +/- 0.3 microM, and a substitution of dThd by IdUrd in the range of 7.1-11.7%. Coadministration of fluorodeoxyuridine did not show significant enhancement of IdUrd-incorporation in granulocytes. Three-day intravenous infusions of IdUrd 1000 mg/sq.m./day produced 1.7-4.5% IdUrd-incorporation in hepatic metastases. Three-day intraarterial infusions (hepatic artery) produced 3.8-10.5% dThd-replacement, whereas, in 9/10 patients this was less than 1% in normal liver. In tumor tissue there was a trend towards FdUrd-modulated enhancement of IdUrd-incorporation, although there was considerable scatter. Cell kinetic studies revealed that IdUrd-incorporation in monocytes and granulocytes was very similar. In lymphocytes, a much lower fraction incorporated IdUrd. Liver tumor contained a considerably higher fraction of IdUrd-labeled cells, compared with normal liver. Potential doubling times for the tumors were estimated to be 10 days.
Speth
P A
PA
Clinical Pharmacology Branch, National Cancer Institute, Bethesda.
Kinsella
T J
TJ
Chang
A E
AE
Klecker
R W
RW
Belanger
K
K
Smith
R
R
Rowland
J
J
Cupp
J E
JE
Collins
J M
JM
D002453:Cell Cycle / Q000528:radiation effects; D003131:Combined Modality Therapy; D004247:DNA / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*
D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D004247:DNA; D007065:Idoxuridine