Glioblastoma multiforme: treatment by large dose fraction irradiation and metronidazole

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)90638-1· OSTI ID:6724368

Kapp, D S; Wagner, F C; Lawrence, R

In an attempt to overcome the possible radioresistance of glioblastoma multiforme related to the large shoulder on the in vitro survival curves and to sensitize hypoxic tumor cells, a treatment protocol was instituted at Yale University Medical Center and affiliated hospitals, using large dose fraction irradiation therapy in conjunction with the hypoxic cell sensitizer metronidazole. Nineteen patients with biopsy-confirmed, previously untreated, cerebral grade IV glioblastoma multiforme were, following surgery, irradiated once a week at 600 rad per fraction, 3.5 to 4 hours after ingestion of metronidazole, 6 gm/m/sup 2/. A total of 7 treatments were employed, with all patients maintained on antiseizure medications and corticosteroids. Metronidazole levels were determined prior to each treatment and patients were followed closely clinically and with serial computerized tomography (CT) scans. The treatment was well tolerated, in general, with no untoward side effects related to the high dose fraction irradiation. The majority of the patients experienced varying degrees of gastrointestinal upset lasting up to several hours following metronidazole administration. Three patients died of pulmonary emboli. One patient experienced moderately severe ototoxicity. A median survival of 9.4 months was obtained for all 19 patients, suggestive of a prolongation of survival compared to historical controls treated with conventionally fractionated radiation or with unconventional radiation fractionation schemes and metronidazole or misonidazole.

• Research Organization: Yale Univ. School of Medicine, New Haven, CT
• OSTI ID: 6724368
• 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.
ALCOHOLS
ANTINEOPLASTIC DRUGS
ASTROCYTOMAS
AZOLES
DISEASES
DRUGS
EVALUATION
FRACTIONATED IRRADIATION
GLIOMAS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIDAZOLES
IRRADIATION
MEDICINE
METRONIDAZOLE
NEOPLASMS
NITRO COMPOUNDS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATIENTS
RADIOLOGY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RADIOTHERAPY
SIDE EFFECTS
SURVIVAL TIME
THERAPY