No abstract

The impact of CNS tumors during childhood and adolescence has been steadily increasing. In many countries, brain and spinal cord tumors are now second in frequency only to leukemia as a cancer affecting children, and the most common cause of cancer mortality in the young. In the United States, brain tumors are now more common than acute lymphoblastic leukemia, and the proportion of cancer deaths due to CNS tumors has nearly doubled during the past 25 years. Worldwide, approximately 30,000-40,000 children develop CNS tumors each year, and the majority do not survive. Compared with most other malignancies that occur during childhood, CNS tumors have not been treated with comparable success in treatment outcome. Also, no specific risk factor, or set of risk factors, has been identified to explain a substantial proportion of CNS tumor occurrence. In many countries, CNS tumors are now the greatest challenge in pediatric oncology.

Twenty-three children with destructive polyarticular juvenile rheumatoid arthritis (JRA) were treated for 0 . 5 4 3 years (median 1.6 years) with weekly doses of methotrexate (MTX) (0.11-0.6 mg/kg/week). Serum levels of MTX at 1 hour and at 24 hours after drug administration were obtained at each dosage level and every 3 months after a stable dosage was achieved. No patient had serum levels of MTX that were in the toxic range nor evidence of hematologic, skin, mucous membrane, gastrointestinal, or pulmonary abnormalities. Ten patients had transiently elevated serum transaminase levels. Arthritis symptoms improved in 21 of these JRA patients, and the improvement was significantly associated with a mean 1-hour serum MTX level of 2 5 . 8 X lO-'M (P = 0.008) and a dosage of 2 0 . 3 mg/kg/week (P = 0.004). The 1-hour serum level of MTX was correlated with the MTX dosage (r = 0.28, P = 0.005).Our observations suggest that with close monitoring, MTX can be used safely at dosages as high as 0.6 mg/kg/ week, and improvement in the symptoms of JRA will become evident when the serum levels of MTX 1 hour after administration approach 6.0 x lO-'M.Methotrexate (MTX) is widely used for the treatment of inflammatory arthritis in adults, and it is