Phase I study of intermittent intravenous bromodeoxyuridine (BUdR) with conventional fractionated irradiation

Journal Article · Sun Jan 01 04:00:00 EST 1984 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(84)90414-0· OSTI ID:6963883

Kinsella, T J; Russo, A; Mitchell, J B; Rowland, J; Jenkins, J; Schwade, J; Myers, C E; Collins, J M; Speyer, J; Kornblith, M D

A Phase I trial of intravenous bromodeoxyuridine (BUdR) and conventional fractionated radiation therapy was performed in 14 patients with glioblastoma multiforme and 7 patients with other poorly radioresponsive tumors. The BUdR was given as a constant intravenous infusion for 12 hr/day for up to 14 days. Local toxicity (within the radiation field) was minor, with 7 of the 21 patients requiring a brief treatment break for moist skin desquamation. There was no significant CNS toxicity noted clinically nor by autopsy examination. Additionally, no significant enhancement of radiation injury was noted to bowel or liver. Dose-dependent systemic toxicity occurred in bone marrow and skin. Moderate myelosuppression, especially thrombocytopenia, was found following a 14 day cycle of BUdR at and above 650 mg/m/sup 2//12 hr infusion. Approximately one-third of patients developed a maculo-papular erythematous rash to the scalp, neck and upper chest. Pharmacology studies revealed steady-state arterial plasma levels of 2 x 10/sup -6/M/1 during the 12 hr infusion of 650 to 700 mg/m/sup 2/. Radiosensitization was measured by a change in the D/sub 0/ of radiation survival curves of human bone marrow CFUc prior to and following the 14 day infusion in 4 patients. A trend of increasing radiosensitization was noted in most patients as the infusion rate of BUdR was increased from 500 to 870 mg/m/sup 2//12 hr. It is concluded that the maximum tolerable dose of BUdR is 650 to 700 mg/m/sup 2//12 hrs when given as a 2 week intermittent intravenous infusion. Local toxicity is acceptable. The major systemic toxicities are myelosuppression and a maculopapular skin rash.

• Research Organization: National Cancer Inst., Bethesda, MD
• OSTI ID: 6963883
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 12:1; 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.
ANIMAL TISSUES
ANTIMETABOLITES
AZINES
BODY
BONE MARROW
BRAIN
BROMOURACILS
BUDR
CENTRAL NERVOUS SYSTEM
CFU
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
FRACTIONATED IRRADIATION
GLIOMAS
HEMATOPOIETIC SYSTEM
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IONIZING RADIATIONS
IRRADIATION
LUNGS
MEDICINE
NEOPLASMS
NERVOUS SYSTEM
NUCLEAR MEDICINE
NUCLEOSIDES
NUCLEOTIDES
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATIENTS
PHARMACOLOGY
PYRIMIDINES
RADIATIONS
RADIOLOGY
RADIOSENSITIVITY EFFECTS
RADIOTHERAPY
RESPIRATORY SYSTEM
RIBOSIDES
SIDE EFFECTS
SKIN
THERAPY
TISSUES
URACILS
X RADIATION