Current and Emerging Chemotherapy Treatment Strategies for Wilms ...

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Current and Emerging Chemotherapy Treatment Strategies for Wilms Tumor in North America. Authors; Authors and affiliations. Eric J. GratiasEmail author ...
Pediatr Drugs 2008; 10 (2): 115-124 1174-5878/08/0002-0115/$48.00/0

THERAPY IN PRACTICE

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Current and Emerging Chemotherapy Treatment Strategies for Wilms Tumor in North America Eric J. Gratias1 and Jeffrey S. Dome2 1 2

Division of Pediatric Hematology/Oncology, T.C. Thompson Children’s Hospital, Chattanooga, Tennessee, USA Division of Pediatric Oncology, Children’s National Medical Center, Washington, District of Columbia, USA

Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 1. Prognostic Factors in Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 1.1 Stage of Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 1.2 Tumor Histology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 1.3 Patient Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 1.4 Tumor Weight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 1.5 Loss of Heterozygosity for 1p and 16q . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 2. Treatment of Wilms Tumor in National Wilms Tumor Studies 1–5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 3. Current Treatment of Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 3.1 Chemotherapy for Favorable Histology Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 3.2 Chemotherapy for Anaplastic Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 3.3 Treatment of Recurrent Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 4. Emerging Strategies for the Treatment of Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 4.1 AREN0532 Study: Very Low, Low, and Standard-Risk Favorable Histology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 4.2 AREN0533 Study: Higher-Risk Favorable Histology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 4.3 AREN0321 Study: High-Risk Renal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 4.4 AREN0631 Study: Recurrent Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

Abstract

Wilms tumor is the most common primary renal malignancy occurring in childhood. Approximately 500 children are diagnosed with Wilms tumor annually in the US alone, most of whom are aged 90% for patients with tumors of favorable histology. However, the treatment of patients with Wilms tumor with anaplastic histology remains challenging. The optimal treatment strategies for Wilms tumor in relapse will be studied via international collaboration in the near future. Goals of emerging studies include minimizing toxicity while maintaining the outstanding cure rates for patients with a good prognosis and, through advancing biologic understanding and developing novel therapeutic approaches, improving the prognosis for those patients in whom effective cure of their disease continues to elude physicians.

Wilms tumor is the most common primary renal malignancy occurring in childhood. Approximately 500 children are diagnosed

with Wilms tumor annually in the US alone, most of whom are aged