[In vitro study on intrathecal application of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant tumor].
To evaluate the possible clinical intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for malignant brain tumors, its anti-tumor activity and neurotoxicity were compared with that of 5-fluorouracil (5-FU) and 5-fluorouridine (FUrd) in vitro. FdUrd showed good tumoricidal activity against cultured mouse 203 glioma cells and rat Walker 256 carcinoma cells as well as A172 human glioblastoma cells. Daoy human medulloblastoma cells and CADO-LC4 human lung cancer cells. It also showed less toxicity for primary cultures of neurons from C57/BL6 mouse and human embryo compared to 5-FU and FUrd. Thymidine phosphorylase (TPase) and thymidine kinase (TK), key enzymes for metabolism of 5-FU derivatives, were measured in cerebrospinal fluid (CSF). TPase or TK activity was detected in the CSF of hardly any patients with malignant brain tumors including meningeal carcinomatosis. These data indicated that the CSF is a favorable site for FdUrd chemotherapy, because the rate of conversion of FdUrd injected to 5-FU would be minimal. In conclusion, FdUrd may be potentially useful for intrathecal treatment of meningeal carcinomatosis.
Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
H
H
Nakagawa
M
M
Yamada
M
M
Fukushima
K
K
Shimizu
K
K
Ikenaka
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D002279:Carcinoma 256, Walker / Q000473:pathology*; D005467:Floxuridine / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007278:Injections, Spinal; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D013937:Thymidine Kinase / Q000134:cerebrospinal fluid; D013939:Thymidine Phosphorylase / Q000134:cerebrospinal fluid; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase; D005472:Fluorouracil