Phase I trial of the combination of 6-methylmercaptopurine riboside and 5-fluorouracil.
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.
Wiemann
M C
MC
Division of Hematology/Oncology, Roger Williams General Hospital Cancer Center, Providence, Rhode Island.
Crabtree
G W
GW
Weitberg
A B
AB
Spremulli
E N
EN
Cummings
F J
FJ
Murray
C
C
Calabresi
P
P
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
D008778:Methylthioinosine; D007288:Inosine; D005472:Fluorouracil