© 2003 by Society
© 2003 by the Society forNeuro-Oncology
A phase I study of topotecan as a radiosensitizer for brainstem glioma ofchildhood: First report of the Children's Cancer Group-0952
University of Wisconsin, Madison, WI 53706 (S.N.S.,M.P.M.); ImClone Systems Inc., Somerville, NJ 08876(M.N.N.); Keck School of Medicine, University ofSouthern California, Los Angeles, CA 90089 (M.D.K.); Children's Hospital and Regional Medical Center, Seattle,WA 98105 (J.R.G.); and M. D. Anderson Cancer Center,Houston, TX 77030 (J.A.)
2 Address correspondence and reprint requests to Minesh P. Mehta, M.D.,Department of Human Oncology, University of Wisconsin Medical School, 600Highland Avenue, K4/3, Madison, WI 53792.
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Abstract |
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Our purpose was to establish the maximum tolerated dosage (MTD) of dailyi.v. topotecan with conventionally fractionated radiotherapy (XRT) forpatients with intrinsic pontine glioma of childhood. Topotecan was given as a30-min i.v. infusion 30-60 min before each XRT treatment given daily for 33days. Total XRT dose was 59.4 Gy. Dose escalation of topotecan was carried outusing a standard phase I design. Dose limiting toxicity (DLT) was defined asan absolute neutrophil count (ANC) of <500/mm3 for >7 days;platelets of <50,000/mm3 for >7 days; >7 days platelettransfusions; fever and neutropenia (ANC <500/mm3 for >7days); and/or any > grade 3 nonhematologic toxicity. In thismulti-institutional phase I study, 17 patients <21 years with intrinsicpontine glioma were enrolled. Sixteen patients completed treatment. An ANC<500/mm3 for >7 days occurred in 2/5 patients at 0.50mg/m2 of topotecan, which was the DLT. The remaining 14 patientsreceived topotecan without experiencing DLT. One patient at 0.40mg/m2 died of disease progression while on treatment. There were 6other grade 4 hematologic events (5 ANCs <500/mm3, 1 hemoglobin<6. 5 g/dl) not meeting DLT criteria. No significant nonhematologictoxicities were seen. The actuarial median survival time is 15 months (95%confidence interval, 9.6-19 months); 1-year survival is 53%. DLT of dailytopotecan with cranial XRT is grade 4 neutropenia for >7 days at 0.50mg/m2 x 33 (total dosage = 16.5 mg/m2); the recommendedsafe MTD of daily topotecan for further phase II testing is 0.40mg/m2 x 33 (total dosage = 13.2 mg/m2).
Received March 14, 2002; Accepted July 16, 2002
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