Abstract
Topotecan appears to be relatively unaffected by the most common multidrug resistance mechanisms, may potentiate cytotoxicity of alkylators, has good penetration into the central nervous system, is active against a variety of neoplasms, and has myelosuppression as its paramount toxicity. We present our experience with a myeloablative regimen that includes topotecan. Twenty-one patients with poor-prognosis tumors and intact function of key organs received topotecan 2 mg/m2 by 30-min intravenous (i.v.) infusion on days −8, −7, −6, −5, −4; thiotepa 300 mg/m2 by 3 h i.v. infusion on days −8, −7, −6; and carboplatin by 4 h i.v. infusion on days −5, −4, −3 with a daily dose derived from the pediatric Calvert formula, using a targeted area under the curve of seven mg/ml* min (∼500 mg/m2/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4) years old; 18 were in complete remission (CR) and three in partial remission (PR). Early toxicities were severe mucositis and erythema with superficial peeling in all patients and a seizure, hypertension, and renal insufficiency followed by veno-occlusive disease in one patient each. Post-transplant treatment included radiotherapy alone (four patients) or plus biological agents (11 patients with neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second CR), and a patient transplanted for multiply recurrent immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results for disease control, manageable toxicity, and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tumors is still uncertain. Bone Marrow Transplantation (2001) 28, 551–556.
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Acknowledgements
This work was supported in part by grants from the National Cancer Institute (CA61017, CA72868), Bethesda, MD; the Robert Steel Foundation, New York, NY; the Katie?s Find A Cure Fund, New York, NY; and the Justin Zahn Fund, New York, NY.
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Kushner, B., Cheung, NK., Kramer, K. et al. Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. Bone Marrow Transplant 28, 551–556 (2001). https://doi.org/10.1038/sj.bmt.1703213
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DOI: https://doi.org/10.1038/sj.bmt.1703213
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