TY - JOUR
T1 - Topotecan is active against Wilms' tumor
T2 - Results of a multi-institutional phase II study
AU - Metzger, Monika L.
AU - Stewart, Clinton F.
AU - Freeman, Burgess B.
AU - Billups, Catherine A.
AU - Hoffer, Fredric A.
AU - Wu, Jianrong
AU - Coppes, Max J.
AU - Grant, Ronald
AU - Chintagumpala, Murali
AU - Mullen, Elizabeth A.
AU - Alvarado, Carlos
AU - Daw, Najat C.
AU - Dome, Jeffrey S.
PY - 2007/7/20
Y1 - 2007/7/20
N2 - 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/m 2). 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.
AB - 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/m 2). 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.
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U2 - 10.1200/JCO.2007.10.9298
DO - 10.1200/JCO.2007.10.9298
M3 - Article
C2 - 17634492
AN - SCOPUS:34547679585
SN - 0732-183X
VL - 25
SP - 3130
EP - 3136
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 21
ER -