Oral zidovudine, continuous-infusion fluorouracil, and oral leucovorin calcium: a phase I study. 1990

M R Posner, and J W Darnowski, and P Calabresi, and I Brunetti, and D Corvese, and G Curt, and F J Cummings, and J Clark, and M J Browne, and J Beitz
Department of Medicine, Roger Williams General Hospital, Providence, RI 02908.

A phase I clinical, pharmacologic, and biochemical evaluation of escalating oral zidovudine (AZT) given over 2 days with a fixed dose of continuous-infusion fluorouracil (800 mg/m2 per day X 3 days) and oral leucovorin calcium was performed. Eighteen patients were treated with doses of AZT ranging from 1.0 to 9.0 g/m2 per day. Nausea and vomiting were dose limiting, with a maximally tolerated dose of 7.5 g/m2 per day. Rash and mucositis occurred but were not dose limiting. A dose-related increase in peak plasma levels of AZT was observed, and the alpha half-life of AZT in plasma (75 min) was unaffected by these high doses. At doses above 4.0 g/m2 per day, trough levels significantly increased, perhaps reflecting prolonged absorption from the gut. No responses were observed; however, a significant increase in DNA single-strand breaks was observed in peripheral blood cells after a threshold dose of 4.0 g/m2 per day, confirming a biological effect of AZT in this regimen. Further trials with an intravenous formulation capable of maintaining plasma levels and circumventing dose-limiting toxicity are warranted.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D002955 Leucovorin The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS. Calcium Leucovorin,Citrovorum Factor,Folinic Acid,N(5)-Formyltetrahydrofolate,5-Formyltetrahydrofolate,5-Formyltetrahydropteroylglutamate,Calcium Folinate,Folinic Acid-SF,Leucovorin, (D)-Isomer,Leucovorin, (DL)-Isomer,Leucovorin, (R)-Isomer,Leucovorin, Calcium (1:1) Salt,Leucovorin, Calcium (1:1) Salt, (DL)-Isomer,Leucovorin, Calcium (1:1) Salt, Pentahydrate,Leucovorin, Monosodium Salt,Leukovorin,Leukovorum,Wellcovorin,5 Formyltetrahydrofolate,5 Formyltetrahydropteroylglutamate,Acid, Folinic,Factor, Citrovorum,Folinate, Calcium,Folinic Acid SF,Leucovorin, Calcium,Monosodium Salt Leucovorin
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D005260 Female Females

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