Methotrexate with thymidine, inosine, and allopurinol rescue: a phase I clinical study

Abstract

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.