Misonidazole as a radiosensitizer in the radiotherapy of glioblastomas and oesophageal cancer. Pharmacokinetic and clinical studies

The British Journal of Radiology
P TamuleviciusC Streffer

Abstract

Since May 1978 the hypoxic-cell radiosensitizer, misonidazole (MIS), has been under clinical investigation in a phase III trial with multiple doses of the drug in 11 patients with brain tumours (seven glioblastomas, four recurrent brain tumours) and three patients with oesophageal carcinoma. The doses of MIS administered were usually well tolerated but the principal toxicities observed were peripheral neuropathy as well as nausea and vomiting was completely reversible. The incidence of neuropathy was not related to the pharmacological parameters of plasma level or half-life. Pharmacological assessment by high-pressure liquid chromatography included assays of plasma, urine and cerebrospinal fluid. The demethylated product, Ro-05-9963, was detected as the major metabolite. Peak plasma levels were obtained one to four hours after administration of MIS, with a half-life of five to ten hours. Cerebrospinal fluid levels of MIS correlated well with those of the plasma. MIS was mainly excreted as the demethylated metabolite, but less than 40% of the given dose could be recovered. The results obtained suggest that the present MIS dosage for glioblastoma patients results in a low plasma level with no observable therapeutic effect.

References

Aug 1, 1979·British Journal of Cancer·R A WhiteN M Bleehen
Feb 1, 1978·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I R FlockhartT R Marten
May 1, 1979·British Journal of Cancer·D V AshR D Bugden
Oct 1, 1979·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R A WhiteN M Bleehen
Jan 1, 1978·International Journal of Radiation Oncology, Biology, Physics·J Denekamp, J F Fowler
Dec 1, 1978·British Journal of Cancer·P WorkmanN M Bleehen
May 1, 1977·British Journal of Cancer·S DischeI R Flockhart
Dec 1, 1976·Cancer Treatment Reviews·J F FowlerJ Denekamp
Apr 1, 1972·The British Journal of Radiology·J F FowlerK Butler

❮ Previous
Next ❯

Citations

Aug 22, 2012·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·C Streffer, T Herrmannn
May 1, 1995·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·M UranoJ Begley
May 1, 1992·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·P TamuelviciusC Streffer

❮ Previous
Next ❯

Related Concepts

Related Feeds

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.