Methotrexate with thymidine, inosine, and allopurinol rescue: a phase I clinical study.
A phase I clinical study of a combination of thymidine (TdR), inosine (IR), and allopurinol used as rescue from 24-hour infusions of methotrexate (MTX) was undertaken following animal studies that had shown a better preservation of antitumor activity with this system than with folinic acid. TdR and IR were given in the dose ratio 5:1 by weight throughout. Rescue from MTX, 400 mg/m2, could be achieved with a TdR dose in the combination of 1 g/m2/24 hours. This same rescue was also effective when the MTX dose was increased to 800 mg/m2, but only partly effective at an MTX dose of 1.5 g/m2. It was not necessary to raise the levels of circulating nucleosides significantly above normal to achieve rescue. MTX-related skin lesions occurred more frequently than might be expected with the MTX dose used.
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007042:Hypoxanthines / Q000097:blood; D007263:Infusions, Parenteral; D007288:Inosine / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D013936:Thymidine / Q000008:administration & dosage; D014527:Uric Acid / Q000097:blood
D007042:Hypoxanthines; D014527:Uric Acid; D007288:Inosine; D000493:Allopurinol; D013936:Thymidine; D008727:Methotrexate