Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation
The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body.
- Research Organization:
- Univ. of California, San Diego
- OSTI ID:
- 5518539
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 11:4
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABDOMEN
RADIATION DOSES
CHEST
FLUOROURACILS
CLEARANCE
RADIOSENSITIVITY EFFECTS
HEAD
NECK
DOSE-RESPONSE RELATIONSHIPS
FRACTIONATED IRRADIATION
LIQUID COLUMN CHROMATOGRAPHY
PATIENTS
SYNERGISM
TOXICITY
ANTIMETABOLITES
AZINES
BODY
BODY AREAS
CHROMATOGRAPHY
DOSES
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IRRADIATION
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
SEPARATION PROCESSES
URACILS
550603* - Medicine- External Radiation in Therapy- (1980-)
550600 - Medicine
560306 - Chemicals Metabolism & Toxicology- Man- (-1987)