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Topotecan Is Active Against Wilms’ Tumor: Results of a Multi-Institutional Phase II Study

Monika L. Metzger, Clinton F. Stewart, Burgess B. Freeman, III, Catherine A. Billups, Fredric A. Hoffer, Jianrong Wu, Max J. Coppes, Ronald Grant, Murali Chintagumpala, Elizabeth A. Mullen, Carlos Alvarado, Najat C. Daw, Jeffrey S. Dome

From the St Jude Children's Research Hospital, Memphis, TN; Texas Children's Hospital, Houston, TX; Dana-Farber Cancer Institute, Boston, MA; Children's Healthcare of Atlanta, Atlanta, GA; Alberta Children's Hospital, Calgary, Alberta; and the Hospital for Sick Children, Toronto, Ontario, Canada

Address reprint requests to Jeffrey S. Dome, MD, Division of Oncology, Center for Cancer and Blood Disorders, Children's National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010-2979; e-mail: jdome{at}cnmc.org

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.

Supported by Grants No. CA-21765 and CA-23099 from the National Institutes of Health, grants from the American Lebanese Syrian Associated Charities of St Jude Children's Research Hospital, and a research grant from GlaxoSmithKline.

Presented in part at the 38th Congress of the International Society of Pediatric Oncology, September 17-21, 2006, Geneva, Switzerland.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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