PURPOSE: A phase II study was designed to determine the efficacy of topotecan, an inhibitor of topoisomerase I, in the treatment of patients with progressive or recurrent pediatric extracranial solid tumors (STs). PATIENTS AND METHODS: Patients younger than 21 years at the time of initial diagnosis with refractory STs were treated with 2 mg/m2 topotecan given by 30-minute infusions for 5 days repeated every 3 weeks. Granulocyte colony stimulating factor (G-CSF) was added to the regimen only after occurrence of severe neutropenia or therapy delay due to sustained neutropenia. RESULTS: One hundred forty-one patients were treated with 539 courses of topotecan. Responses were seen in 34 patients (3 had complete responses [CRs], 2 had partial responses [PRs], and 24 had minor responses [MRs] or stable disease [SD]). The number of administered courses in patients with SD varied between 5 and 24, with a median of 10. The median time on the study for patients with SD was approximately 8.5 months. In patients without bone marrow involvement, the most frequent toxicity was myelosuppression: hemoglobin < 8 g/dl in 83 of 341 courses, absolute granulocyte count < 1,000/microl in 221 of 341 courses, and platelet count < 50,000/microl in 162 of 341 courses. Nausea and vomiting were infrequent; many patients were pretreated with ondansetron or granisetron. A recurrent rash developed in 16 patients and was usually well controlled with diphenhydramine and hydrocortisone. G-CSF was administered in 203 of 539 courses because of neutropenia. Therapy was delayed over 1 week in 33 instances. CONCLUSION: In previously treated patients, topotecan produced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma. In hepatoblastoma, rhabdomyosarcoma, and a few rare tumors, long-lasting MRs and SDs with excellent symptom control were seen. The toxicity of topotecan, predominantly myelosuppression, was tolerable.
PURPOSE: A phase II study was designed to determine the efficacy of topotecan, an inhibitor of topoisomerase I, in the treatment of patients with progressive or recurrent pediatric extracranial solid tumors (STs). PATIENTS AND METHODS: Patients younger than 21 years at the time of initial diagnosis with refractory STs were treated with 2 mg/m2 topotecan given by 30-minute infusions for 5 days repeated every 3 weeks. Granulocyte colony stimulating factor (G-CSF) was added to the regimen only after occurrence of severe neutropenia or therapy delay due to sustained neutropenia. RESULTS: One hundred forty-one patients were treated with 539 courses of topotecan. Responses were seen in 34 patients (3 had complete responses [CRs], 2 had partial responses [PRs], and 24 had minor responses [MRs] or stable disease [SD]). The number of administered courses in patients with SD varied between 5 and 24, with a median of 10. The median time on the study for patients with SD was approximately 8.5 months. In patients without bone marrow involvement, the most frequent toxicity was myelosuppression: hemoglobin < 8 g/dl in 83 of 341 courses, absolute granulocyte count < 1,000/microl in 221 of 341 courses, and platelet count < 50,000/microl in 162 of 341 courses. Nausea and vomiting were infrequent; many patients were pretreated with ondansetron or granisetron. A recurrent rash developed in 16 patients and was usually well controlled with diphenhydramine and hydrocortisone. G-CSF was administered in 203 of 539 courses because of neutropenia. Therapy was delayed over 1 week in 33 instances. CONCLUSION: In previously treated patients, topotecan produced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma. In hepatoblastoma, rhabdomyosarcoma, and a few rare tumors, long-lasting MRs and SDs with excellent symptom control were seen. The toxicity of topotecan, predominantly myelosuppression, was tolerable.
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