title: 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.
abstract: OBJECTIVE
  To determine the optimal duration of preoperative chemotherapy to further increase the proportion of stage I tumors by comparison of two regimens in the treatment of patients older than 6 months who have unilateral Wilms' tumor.
  
  
  METHODS
  Eligible patients (n = 382) initially received four weekly 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 receive 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 histology 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 and favorable or standard histology, VCR, AMD, and an anthracycline for 27 weeks (AVE) with no abdominal radiotherapy for stage II N0 disease (n = 75) or with a 15-Gy dose of abdominal irradiation (RTH) in case of stages IIN1 and III (n = 56). Anaplastic tumors staged higher than I or clear-cell sarcoma of the kidney (14), AMD, VCR, an anthracycline, and ifosfamide for 36 weeks (DEVI).
  
  
  RESULTS
  No advantage was found in favor of prolonged preoperative treatment. The percentages obtained for the 4-week and the 8-week groups, respectively, were as follows: stage I, 64% versus 62%; intraoperative tumor rupture 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 treatment groups were as follows: NFT, 100% for both EFS and OS; AV, 88% and 93%; AVE, 84% and 88%; AVE RTH, 71% and 85%; and DEVI, 71% and 71%. The rate of abdominal recurrences in stage II N0 nonirradiated patients was 6.6%.
  
  
  CONCLUSIONS
  The 4-week schedule pre-nephrectomy chemotherapy regimen should be considered the standard treatment. Clinical trials should continue to improve the cure rate of high-risk patients and the quality of life of children with a more favorable prognosis.
authors.affiliation: Institut Gustave-Roussy, Villejuif, France. tournade@igr.fr
authors.forename: M F
authors.initials: MF
authors.lastname: Tournade
authors.forename: C
authors.initials: C
authors.lastname: Com-Nougué
authors.forename: J
authors.initials: J
authors.lastname: de Kraker
authors.forename: R
authors.initials: R
authors.lastname: Ludwig
authors.forename: A
authors.initials: A
authors.lastname: Rey
authors.forename: J M
authors.initials: JM
authors.lastname: Burgers
authors.forename: B
authors.initials: B
authors.lastname: Sandstedt
authors.forename: J
authors.initials: J
authors.lastname: Godzinski
authors.forename: M
authors.initials: M
authors.lastname: Carli
authors.forename: R
authors.initials: R
authors.lastname: Potter
authors.forename: J M
authors.initials: JM
authors.lastname: Zucker
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003609:Dactinomycin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D009392:Nephrectomy; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage; D009396:Wilms Tumor / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
chemical_list: D000903:Antibiotics, Antineoplastic; D003609:Dactinomycin; D014750:Vincristine