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Friday 01 August 2003

Oral topotecan for refractory and relapsed neuroblastoma: a retrospective analysis.

By: Kramer K, Kushner BH, Cheung NK.

J Pediatr Hematol Oncol 2003 Aug;25(8):601-5

PURPOSE: Among patients with multiply relapsed neuroblastoma refractory to conventional chemotherapy, oral topotecan has often been used for palliation. Although toxicity was generally thought to be mild, the efficacy of such an approach remains unproven. METHODS: The authors retrospectively analyzed patients with multiply relapsed or refractory neuroblastoma who were treated with oral topotecan for palliation. Each course was generally 1 mg/m2/d in two divided doses, for 21 consecutive days, repeated after a 1-week rest in patients without symptoms of progressive disease. Disease status was assessed by radiographic studies, urine catecholamine levels, and multiple bone marrow aspirations and biopsies. RESULTS: Twenty patients between the ages of 3 and 34 (median 13 years) received 1 (n = 7), 2 (n = 3), 3 (n = 4), 4 (n = 2), 6 (n = 2), and 12 courses (n = 2). Prior treatments included multiple cycles of high-dose alkylator-based chemotherapy (n = 20), high-dose intravenous topotecan (n = 8), myeloablative chemotherapy or radioimmunotherapy (n = 10), or experimental biologic agents (n = 16). Anti-neuroblastoma effects were seen in five patients lasting 6 to 12 months; two additional patients remained stable for 4 months. Thirteen patients had progressive disease (11 after one or two cycles). Toxicity included diarrhea (n = 12) requiring a dose adjustment in three patients and discontinuation of the drug in a fourth, and myelosuppression (n = 11) requiring transfusion and/or granulocyte-colony stimulating factor support.CONCLUSIONS: Oral topotecan therapy has antitumor activity in a small percentage of patients with relapsed or refractory neuroblastoma. Toxicities, including diarrhea and myelosuppression, may necessitate a dose adjustment in this patient population. Low-dose oral topotecan may have utility in the treatment of neuroblastoma.

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