Topotecan is active against Wilms' tumor: results of a multi-institutional phase II study
Autor: | Monika L. Metzger, Burgess B. Freeman, Najat C. Daw, Elizabeth Mullen, Fredric A. Hoffer, Jeffrey S. Dome, Clinton F. Stewart, Max J. Coppes, Ronald Grant, Catherine A. Billups, Murali Chintagumpala, Jianrong Wu, Carlos Alvarado |
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Rok vydání: | 2007 |
Předmět: |
Male
Cancer Research medicine.medical_specialty Maximum Tolerated Dose Urology Phases of clinical research Risk Assessment Wilms Tumor Disease-Free Survival Drug Administration Schedule medicine Humans Child Infusions Intravenous Survival analysis Neoplasm Staging Dose-Response Relationship Drug business.industry Area under the curve Wilms' tumor medicine.disease Prognosis Immunohistochemistry Survival Analysis Kidney Neoplasms Surgery Clinical trial Regimen Treatment Outcome Oncology Area Under Curve Child Preschool Topotecan Female Neoplasm Recurrence Local business Kidney disease medicine.drug |
Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 25(21) |
ISSN: | 1527-7755 |
Popis: | Purpose A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor. Patients and Methods Patients with favorable histology Wilms' tumor (FHWT) and recurrence after at least one salvage chemotherapy regimen or with anaplastic histology Wilms' tumor (AHWT) in first or subsequent recurrence were eligible. Patients were stratified according to histology, with statistical considerations based on the FHWT stratum. Topotecan was administered intravenously over 30 minutes for 5 days on 2 consecutive weeks. Treatment dosages were adjusted to achieve a target area under the curve (AUC) of 80 ± 10 ng/mL*h. Tumor responses were measured after two cycles of treatment. Results Thirty-seven patients (26 patients with FHWT) were enrolled and received a total of 94 cycles of topotecan (range, one to six cycles). The median topotecan dosage required to achieve the target AUC was 1.8 mg/m2 (range, 0.7 to 3.2 mg/m2). Of 25 assessable patients with FHWT, 12 had partial response (PR), six had stable disease (SD), and seven had progressive disease (PD), for an overall response rate of 48% (95% CI, 27.8% to 68.7%). Of 11 assessable patients with AHWT, two had PR, one had SD, and eight had PD. The main toxicities were grade 3 and 4 neutropenia (median duration, 13 days) and thrombocytopenia (median duration, 7.5 days). Conclusion Topotecan administered on a protracted schedule is active against recurrent FHWT. Inclusion of topotecan in front-line clinical trials for patients with recurrent Wilms' tumor should be considered. |
Databáze: | OpenAIRE |
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