The importance of dosage in the treatment of mouse leukemia with a-methopterin (Methotrexate) has been demonstrated by Goldin and associates.1 They found in the treatment of leukemia L 1210 that a schedule of large, infrequent doses of a-methopterin was, with regard to survival time, therapeutically superior to single maximum doses or to small, consecutive daily doses, if treatment was begun soon after tumor implantation. The optimum interval of four days between consecutive doses was subsequently shown to be closely related to the time required for recovery of the mouse from the effects of the drug.2 The enhanced therapeutic effectiveness of this intermittent regimen suggested that the host recovered faster than the tumor, so that the tumor was damaged selectively by subsequent doses of the drug.
The therapeutic advantage of this dosage regimen was so obvious that its clinical application was undertaken. Studies in man led to the selection
Condit PT, Eliel LP. EFFECTS OF LARGE INFREQUENT DOSES OF A-METHOPTERIN ON ACUTE LEUKEMIA IN CHILDREN. JAMA. 1960;172(5):451-453. doi:10.1001/jama.1960.63020050004013