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6-Mercaptopurine in Childhood Leukemia^*

Comparison of Large Dose Interrupted with Small Dose Continuous Therapy

Carol B. Hyman, Charles Brubaker and Phillip Sturgeon

( Hematology Research Laboratories, Childrens Hospital and the Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, Calif.)

1. The results of treatment of acute lymphatic leukemia in children with 6-MP with large dose-interrupted therapy of 6.6 mg/kg/day (3 mg/lb/day) compared with small dose-continuous therapy with 2.2 mg/kg/day (1 mg/lb/day) are described.

2. The intervals from the start of therapy to onset of drug effect and onset of remission were shorter with the larger dose.

3. The duration of remission in this study was longer with continuous therapy.

4. Toxicity associated with a dose of 6.6 mg/kg/day (3 mg/lb/day) appeared after 3–32 days of treatment, but serious toxicity was not encountered for the first 16 days.

5. The combination of 6.6 mg/kg/day (3 mg/lb/day) of 6-MP and 1.1 mg/kg/day (0.5 mg/lb/day) of azaserine was given to a small series of patients. Because of severe gastrointestinal toxicity, additional studies were not carried out.

6. The results of this study suggest that 6-MP could be used to better advantage if for the first 2 weeks of treatment 6.6 mg/kg/day (3 mg/lb/day) were given and then the dose changed to 2.2 mg/kg/day (1 mg/lb/day) for maintenance therapy. In this way, the latent period preceding the onset of remission would be shortened, and the benefits of continuous therapy preserved.

^* This work was supported in part by Grant CY-2649 (R) from the National Cancer Institute of the National Institutes of Health, the Alexander and Margaret Stewart Trust, and the Leukemia Research Foundation of California.

Markle Scholar in Medical Sciences.

Received 4/22/57.