Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: Results of the ninth International Society of Pediatric Oncology Wilms' tumor trial and study

Purpose: To determine the optimal duration of preoperative chemotherapy to further increase the proportion of stage I tumors by comparison of two regi mens in the treatment of patients older than 6 months who have unilateral W ilms' tumor. Patients and Methods: Eligible patients (n = 382) initially received four w eekly doses of vincristine (VCR) and two courses of actinomycin D (AMD) and were randomized either to be operated on (4-week group [n = 193]) or to re ceive 4 more weeks of the same chemotherapy regimen (8-week group [n = 189] ). The assessment criterion was the observed percentage of stage I tumors. After surgery, patients were assigned according to tumor stage and histolog y to four different treatment groups: stage I and favorable histology (n = 5) were to have no further treatment (NFT); stage I and standard histology or anaplasia (n = 244), VCR and AMD for 17 weeks (AV); stages II and III an d favorable or standard histology, VCR, AMD, and an anthracycline for 27 we eks (AVE) with no abdominal radiotherapy for stage II N0 disease (n = 75) o r with a 15-Gy dose of abdominal irradiation (RTH) in case of stages IIN1 a nd III (n = 56). Anaplastic tumors staged higher than I or clear-cell sarco ma of the kidney (14), AMD, VCR, an anthracycline, and ifosfamide for 36 we eks (DEVI). Results: No advantage wets found in favor of prolonged preoperative treatme nt. The percentages obtained for the 4-week and the 8-week groups, respecti vely, were as follows: stage I, 64% versus 62%; intraoperative tumor ruptur e rate, 1% versus 3%; 2-year EFS, 84% versus 83%; and 5-year OS, 92% versus 87%. Two-year EFS and 5-year OS rates, respectively, of the different trea tment groups were as follows: NFT, 100% for both EFS and OS; AV, 88% and 93 %; AVE, 84% and 88%; AM RTH, 71% and 85%; and DM, 71% and 71%. The rate of abdominal recurrences in stage II NO nonirradiated patients was 6.6%. Conclusion: The 4-week schedule pre-nephrectomy chemotherapy regimen should be considered the standard treatment. Clinical trials should continue to i mprove the cure rate of high-risk patients and the quality of life of child ren with ct more favorable prognosis. J Clin Oncol 19:488-500. (C) 9001 by American Society of Clinical Oncology.