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

Journal Article · Mon Mar 01 00:00:00 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), Vol. 8:3/4
• Country of Publication: United States
• Language: English

Related Subjects

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