Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in childrenand young adults

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/m(2) by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4; thiotepa 300 mg/m(2) 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 und er the curve of seven mg/ml* min (similar to 500 mg/m(2)/day). Stem cell re scue 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 toxic ities were severe mucositis and erythema with superficial peeling in all pa tients and a seizure, hypertension, and renal insufficiency followed by ven o-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, eve nt-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brai n tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sa rcoma (first or second CR), and a patient transplanted for multiply recurre nt immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results fo r disease control, manageable toxicity, and the antitumor profiles of topot ecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tum ors is still uncertain.