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Volume 328:1725-1731 June 17, 1993 Number 24 Next

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ABSTRACT

Background Among patients with malignant brain tumors, infants and very young children have the worst prognosis and the most severe treatment-related neurotoxic effects. Therefore, in 1986, the Pediatric Oncology Group began a study in which postoperative chemotherapy was given in order to permit a delay in the delivery of radiation to the developing brain.

Methods Children under 36 months of age with biopsy-proved malignant brain tumors were treated postoperatively with two 28-day cycles of cyclophosphamide plus vincristine, followed by one 28-day cycle of cisplatin plus etoposide. This sequence was repeated until the disease progressed or for two years in 132 children under 24 months of age at diagnosis and for one year in 66 children 24 to 36 months of age at diagnosis. After this, the patients received radiation therapy. The response to the first two cycles of chemotherapy was measured in 102 patients with residual postoperative disease.

Results The first two cycles of cyclophosphamide and vincristine produced complete or partial responses in 39 percent of the 102 patients who could be evaluated. The response rates were highest among patients with medulloblastomas, malignant gliomas, or ependymomas. Patients with brain-stem gliomas or embryonal tumors (primitive neuroectodermal tumors) had little or no response. The progression-free survival rate was 41 percent at one year for children who were 24 to 36 months old at diagnosis and 39 percent at two years for those under 24 months of age at diagnosis. Multivariate analysis identified embryonal tumors as a significant adverse prognostic feature (relative risk, 2.2; 95 percent confidence interval, 1.4 to 3.4) and complete resection as a favorable feature (relative risk, 0.33; 95 percent confidence interval, 0.20 to 0.54). Complete responses to chemotherapy were associated with a progression-free survival rate approaching that achieved with gross total resection. A comparison of cognitive evaluations obtained at base line and after one year of chemotherapy revealed no evidence of deterioration in cognitive function.

Conclusions Chemotherapy appears to be an effective primary postoperative treatment for many malignant brain tumors in young children. Disease control for one or two years in a large minority of patients permitted a delay in the delivery of radiation and, on the basis of preliminary results, a reduction in neurotoxicity. For patients who had undergone total surgical resection or who had a complete response to chemotherapy, the results are sufficiently encouraging to suggest that radiation therapy may not be needed in this subgroup of children after at least one year of chemotherapy.

Source Information

From the State University of New York at Buffalo School of Medicine and Biomedical Sciences and the Roswell Park Cancer Institute, Buffalo (P.K.D., M.E.C.); the Pediatric Branch of the National Cancer Institute, Bethesda, Md. (M.E.H.); the Pediatric Oncology Group Statistical Office, University of Florida, Gainesville (J.P.K.); Duke University Medical Center, Durham, N.(H.S.F., P.C.B.); St. Jude Children's Research Hospital, Memphis, Tenn. (R.A.S., R.K.M., L.E.K.); Children's Mercy Hospital, Kansas City, Mo. (F.G.S.); University of California Medical Center, San Diego (H.E.J.); and Montreal General Hospital, Montreal (C.R.F.).

Address reprint requests to Dr. Duffner at the Pediatric Oncology Group Operations Office (8633, 8634), 4949 W. Pine Blvd., St. Louis, MO 63108.

Full Text of this Article

Related Letters:

Brain Tumors in Infants
Jenkin D., Longcope J. C., Watson S. S., Duffner P. K., Allen J. C., Kun L. E.
Extract | Full Text  
N Engl J Med 1993; 329:1963-1964, Dec 23, 1993. Correspondence

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