Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults Journal Article
| Authors: | Kushner, B. H.; Cheung, N. K. V.; Kramer, K.; Dunkel, I. J.; Calleja, E.; Boulad, F. |
| Article Title: | Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults |
| 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. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; treatment outcome; child, preschool; clinical trial; cisplatin; doxorubicin; area under the curve; drug penetration; drug potentiation; hypertension; solid tumor; combined modality therapy; radiotherapy, adjuvant; topotecan; brain tumor; follow up; brain neoplasms; neoplasm; carboplatin; metastasis; controlled clinical trial; liver toxicity; bone marrow suppression; etoposide; mucosa inflammation; antineoplastic combined chemotherapy protocols; granulocyte macrophage colony stimulating factor; alkylating agent; cyclophosphamide; melphalan; vincristine; kidney failure; stem cell transplantation; hematopoietic stem cell transplantation; thiotepa; childhood cancer; central nervous system; monoclonal antibody; ewing sarcoma; disease severity; infant; neuroblastoma; experience; dactinomycin; erythema; remission; remission induction; bleomycin; drug toxicity; seizure; drug cytotoxicity; disease control; ovary teratoma; granulocyte colony stimulating factor; retinoic acid; multidrug resistance; desmoplastic small round cell tumor; brain tumors; skin abrasion; vein occlusion; myeloablative agent; pediatric solid tumors; humans; prognosis; human; male; female; priority journal; article; myeloablative therapy |
| Journal Title: | Bone Marrow Transplantation |
| Volume: | 28 |
| Issue: | 6 |
| ISSN: | 0268-3369 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-09-01 |
| Start Page: | 551 |
| End Page: | 556 |
| Language: | English |
| DOI: | 10.1038/sj.bmt.1703213 |
| PUBMED: | 11607767 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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