Application in radiation therapy of substances which modify cellular radiation response. [Metronidazole]

Conference · Fri Jul 01 04:00:00 EDT 1977 · Cancer; (United States)

OSTI ID:7300330

Chapman, J D; Urtasun, R C

Compounds to be considered as potential adjuvants in radiotherapy should indicate a strong mechanistic rationale for a differential response between tumor and normal tissues. Drugs which selectively radiosensitize hypoxic cells might be exploited in radiotherapy to increase the sterilization of resistant hypoxic areas of solid tumors which have outgrown their vascular supply. Several compounds have been shown to selectively radiosensitize hypoxic mammalian cells in vitro but their application in clinical studies is presently limited by their toxicity at the high drug dosages required to effect the sensitization. Phase I and Phase II clinical studies have now been completed with the sensitizer, metronidazole. This drug was tolerated by patients at dosages of 6 g/m/sup 2/ three times a week for 3 weeks with a minimum of side effects, and survival of patients with glioblastoma multiforme treated with fractionated radiotherapy was significantly increased when the sensitizer was used in combination with the radiation. Drugs which selectively radioprotect oxygenated cells might also be exploited in therapy by permitting the use of higher radiation doses and thereby incurring more damage to the resistant hypoxic cells in tumors. Again, drug toxicity appears to be a limiting factor with this approach. If toxicities are not additive, combinations of radiosensitizers and radioprotectors might prove more effective than either individual approach.

• Research Organization: Whiteshell Nuclear Research Establishment, Pinawa, Manitoba
• OSTI ID: 7300330
• Conference Information: Journal Name: Cancer; (United States) Journal Volume: 40(suppl.):1
• Country of Publication: United States
• Language: English

Related Subjects

560151* -- Radiation Effects on Animals-- Man
560306 -- Chemicals Metabolism & Toxicology-- Man-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMAL CELLS
ANOXIA
AZOLES
CRYOGENIC FLUIDS
DISEASES
DRUGS
ELEMENTS
FLUIDS
FRACTIONATED IRRADIATION
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIDAZOLES
IRRADIATION
MEDICINE
METRONIDAZOLE
NEOPLASMS
NITRO COMPOUNDS
NONMETALS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN
PATIENTS
RADIOLOGY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RADIOTHERAPY
RESPONSE MODIFYING FACTORS
THERAPY
TOXICITY
TUMOR CELLS