Current Clinical Trials

Children with relapsed favorable-histology Wilms tumor have a variable prognosis, depending on the site of relapse, the time from initial diagnosis to relapse, and their previous therapy. Favorable prognostic factors include no prior treatment with doxorubicin, relapse more than 12 months after diagnosis, and intra-abdominal relapse in a patient not previously treated with abdominal radiation.[1-3]

Wilms tumor patients whose initial therapy consisted of immediate nephrectomy followed by chemotherapy with vincristine and dactinomycin who relapse can be successfully retreated. Fifty eight patients were treated on NWTS-5 relapse protocol with surgical excision when feasible, radiation therapy and alternating courses of vincristine, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. Four year EFS after relapse was 71% and overall survival was 82%. For those patients who relapsed only to their lungs the 4 year EFS after relapse was 68% and OS was 81%.[4] Approximately 50% of unilateral Wilms tumor patients who relapse or progress after initial treatment with vincristine, dactinomycin and doxorubicin and radiation can be successfully retreated. Sixty patients were treated on the NWTS-5 relapse protocol with alternating courses of cyclophosphamide/etoposide and carboplatin/etoposide, surgery and radiation therapy. EFS (4 year) and OS were 42% and 48%, respectively, and 49% and 53% for patients who relapsed in the lungs only.[5]

Patients with stages II–IV anaplastic-histology tumors at diagnosis have a very poor prognosis upon recurrence.[6] The combination of ifosfamide, etoposide, and carboplatin has demonstrated activity in this group of patients, but significant hematologic toxic effects have been observed.[7,8] While high-dose chemotherapy followed by autologous hematopoietic stem cell transplant has been utilized,[9-11] an intergroup study of the former Pediatric Oncology Group (POG) and the former Children’s Cancer Group used a salvage induction regimen of cyclophosphamide and etoposide (CE) alternating with carboplatin and etoposide (PE) followed by delayed surgery. Disease-free patients were assigned to maintenance chemotherapy with five cycles of alternating CE and PE, and the remainder of patients to ablative therapy and autologous marrow transplant. All patients received local radiation therapy. The 3-year survival was 52% for all eligible patients, while the 3-year survival was 64% and 42% for the chemotherapy consolidation and autologous marrow transplant subgroups, respectively.[3] The outcome of hematopoietic stem cell rescue in selected patients may be superior, [11] however, patients with gross residual disease going into transplant do not do as well.[9] Patients in whom such salvage attempts fail should be offered treatment on available phase I or phase II studies.

Treatment of patients with recurrent clear cell sarcoma of the kidney depends on initial therapy. Cyclophosphamide and carboplatin should be considered if not used initially. Patients with recurrent CCSK involving the brain have responded to treatment with ifosfamide, carboplatin and etoposide (ICE) coupled with local control consisting of either surgical resection and /or radiation.[12] Patients with recurrent rhabdoid tumor of the kidney, clear cell sarcoma of the kidney, neuroepithelial tumor of the kidney, and renal cell carcinoma should be considered for treatment on available phase I and phase II clinical trials.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent Wilms tumor and other childhood kidney tumors. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Grundy P, Breslow N, Green DM, et al.: Prognostic factors for children with recurrent Wilms' tumor: results from the Second and Third National Wilms' Tumor Study. J Clin Oncol 7 (5): 638-47, 1989.  [PUBMED Abstract]
   
   
2. Malogolowkin M, Bergman T, Seibel N, et al.: Outcome and prognostic factors (PF) for patients with recurrent Wilms tumor (R-WT) National Wilms Tumor Study 3 and 4 (NWTS 3,4). [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-3136, 2001. 
   
   
3. Tannous R, Giller R, Holmes E, et al.: Intensive therapy for high risk (HR) relapsed Wilms' tumor (WT): a CCG-4921/POG-9445 study report. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A2315, 2000. 
   
   
4. Green DM, Cotton CA, Malogolowkin M, et al.: Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 48 (5): 493-9, 2007.  [PUBMED Abstract]
   
   
5. Malogolowkin M, Cotton CA, Green DM, et al.: Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 50 (2): 236-41, 2008.  [PUBMED Abstract]
   
   
6. Dome JS, Cotton CA, Perlman EJ, et al.: Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol 24 (15): 2352-8, 2006.  [PUBMED Abstract]
   
   
7. Abu-Ghosh AM, Krailo MD, Goldman SC, et al.: Ifosfamide, carboplatin and etoposide in children with poor-risk relapsed Wilms' tumor: a Children's Cancer Group report. Ann Oncol 13 (3): 460-9, 2002.  [PUBMED Abstract]
   
   
8. Kung FH, Bernstein ML, Camitta BM, et al.: Ifosfamide/carboplatin/etoposide (ICE) in the treatment of advanced, recurrent Wilms tumor. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A-2156, 559a, 1999. 
   
   
9. Garaventa A, Hartmann O, Bernard JL, et al.: Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry. Med Pediatr Oncol 22 (1): 11-4, 1994.  [PUBMED Abstract]
   
   
10. Pein F, Michon J, Valteau-Couanet D, et al.: High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell rescue in pediatric high-risk recurrent Wilms' tumor: a French Society of Pediatric Oncology study. J Clin Oncol 16 (10): 3295-301, 1998.  [PUBMED Abstract]
    
    
11. Campbell AD, Cohn SL, Reynolds M, et al.: Treatment of relapsed Wilms' tumor with high-dose therapy and autologous hematopoietic stem-cell rescue: the experience at Children's Memorial Hospital. J Clin Oncol 22 (14): 2885-90, 2004.  [PUBMED Abstract]
    
    
12. Radulescu VC, Gerrard M, Moertel C, et al.: Treatment of recurrent clear cell sarcoma of the kidney with brain metastasis. Pediatr Blood Cancer 50 (2): 246-9, 2008.  [PUBMED Abstract]
    
    

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