Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer

Journal Article · Mon Oct 01 04:00:00 EDT 1984 · J. Clin. Oncol.; (United States)

OSTI ID:5615268

Kinsella, T J; Mitchell, J B; Russo, A; Aiken, M; Morstyn, G; Hsu, S M; Rowland, J; Glatstein, E

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 x 10(-7) mol/L and 1 x 10(-6) mol/L during infusion of 650 and 1000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). The authors conclude that local and systemic toxicity of continuous infusion of BUdR at 1000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.

• Research Organization: National Cancer Inst., Bethesda, MD
• OSTI ID: 5615268
• Journal Information: J. Clin. Oncol.; (United States), Journal Name: J. Clin. Oncol.; (United States) Vol. 2:10; ISSN JCOND
• Country of Publication: United States
• Language: English

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550603* -- Medicine-- External Radiation in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMAL TISSUES
ANTIBODIES
AZINES
BODY
BONE MARROW
CFU
DISEASES
HEMATOPOIETIC SYSTEM
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INJECTION
INTAKE
INTRAVENOUS INJECTION
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NEOPLASMS
NUCLEAR MEDICINE
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATIENTS
PYRIMIDINES
RADIOLOGY
RADIOSENSITIVITY EFFECTS
RADIOTHERAPY
RIBOSIDES
SKIN
SURVIVAL CURVES
THERAPY
TISSUES
TOXICITY
TUMOR CELLS
URACILS
URIDINE