High dose misonidazole with dexamethasone rescue: a possible approach to circumvent neurotoxicity

Journal Article · Mon Mar 01 04:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90641-1· OSTI ID:6711630

Urtasun, R C; Tanasichuk, H; Fulton, D; Agboola, O; Turner, A R; Koziol, D; Raleigh, J

With a view of modifying misonidazole (MISO) neurotoxicity, we initiated a randomized clinical study to assess a possible drug interaction and toxicity protection when dexamethasone (DXM) is administered concomitantly with MISO. The ongoing study consists of: 1. Pharamacokinetic evaluation; 2. Assessment of toxicity. Fourteen patients undergoing radiation therapy for different types of malignant neoplasia (excluding brain tumors) have been randomized to receive either MISO alone, or DXM one week prior and during treatment with MISO. Five of seven patients receiving MISO alone developed peripheral neuropathies while only one out of 7 patients that received MISO with DXM coverage developed a transient and mild neuropathy. Pharmacokinetic evaluation of MISO in plasma and urine of those patients receiving DXM has shown no evidence of drug interaction. It is postulated that the mechanism of action of DXM is at the nerve cell membrane level, restoring and stabilizing cell surface properties. In future studies we will investigate the use of DXM with increasing doses of MISO above the recommended maximum dose of 12 gm/m/sup 2/, hoping to achieve a higher tumor tissue level of MISO while avoiding unacceptable toxicity. The effect of Allopurinol on the plasma kinetics of MISO was studied in four additional patients, observing also no evidence of drug interaction.

• Research Organization: Univ. of Alberta, Edmonton, Alberta, Canada
• OSTI ID: 6711630
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:3/4; ISSN IOBPD
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADRENAL HORMONES
ANIMAL CELLS
ANTINEOPLASTIC DRUGS
AZOLES
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CELL MEMBRANES
CORTICOSTEROIDS
DEXAMETHASONE
DISEASES
DRUGS
GLUCOCORTICOIDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
IMIDAZOLES
KETONES
KINETICS
MEDICINE
MEMBRANES
MISONIDAZOLE
NEOPLASMS
NERVE CELLS
NERVOUS SYSTEM
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATIENTS
PHARMACOLOGY
PREGNANES
RADIOLOGY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RADIOTHERAPY
SOMATIC CELLS
STEROID HORMONES
STEROIDS
SYNERGISM
THERAPY
TOXICITY