title: Phase I trial of the combination of 6-methylmercaptopurine riboside and 5-fluorouracil.
abstract: 6-Methylmercaptopurine riboside (MMPR) and 5-fluorouracil (5-FU) were administered sequentially to 12 patients in a phase I clinical trial. Toxicities included mild nausea and vomiting, as well as reversible leukopenia and thrombocytopenia. Maximal accumulation of 6-methylmercaptopurine ribonucleoside 5'-monophosphate (MMPR-P), the active metabolite of MMPR, in patients' erythrocytes occurred between 2 and 6 h after the administration of MMPR and the degree of accumulation was dose-related. At 96 h after MMPR administration, MMPR-P was still detectable in patients' erythrocytes. Although no clinical responses were documented, a modified dosage schedule of these drugs should be pursued based on the pharmacokinetic data obtained.
authors.affiliation: Division of Hematology/Oncology, Roger Williams General Hospital Cancer Center, Providence, Rhode Island.
authors.forename: M C
authors.initials: MC
authors.lastname: Wiemann
authors.forename: G W
authors.initials: GW
authors.lastname: Crabtree
authors.forename: A B
authors.initials: AB
authors.lastname: Weitberg
authors.forename: E N
authors.initials: EN
authors.lastname: Spremulli
authors.forename: F J
authors.initials: FJ
authors.lastname: Cummings
authors.forename: C
authors.initials: C
authors.lastname: Murray
authors.forename: P
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007288:Inosine / Q000031:analogs & derivatives*; D008297:Male; D008778:Methylthioinosine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008875:Middle Aged
chemical_list: D008778:Methylthioinosine; D007288:Inosine; D005472:Fluorouracil