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
Sep 1, 1979·British Journal of Cancer·P Workman
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
May 1, 1978·Journal of Chromatography·P WorkmanN M Bleehen
Dec 1, 1978·British Journal of Cancer·P WorkmanN M Bleehen
Mar 1, 1976·The British Journal of Radiology·R JohnsonD Boyle
Mar 1, 1977·Radiology·R C UrtasunC G Fryer
May 1, 1977·British Journal of Cancer·S DischeI R Flockhart
Dec 1, 1976·Cancer Treatment Reviews·J F FowlerJ Denekamp
Jun 1, 1975·British Journal of Cancer·J L FosterC E Smithen
Apr 1, 1972·The British Journal of Radiology·J F FowlerK Butler
Citations
Nov 1, 1983·The British Journal of Radiology·N M BleehenA E Holmes
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