title: Topotecan is active against Wilms' tumor: results of a multi-institutional phase II study.
abstract: OBJECTIVE
  A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: St Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Monika L
authors.initials: ML
authors.lastname: Metzger
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Burgess B
authors.initials: BB
authors.lastname: Freeman
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Billups
authors.forename: Fredric A
authors.initials: FA
authors.lastname: Hoffer
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.forename: Max J
authors.initials: MJ
authors.lastname: Coppes
authors.forename: Ronald
authors.initials: R
authors.lastname: Grant
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mullen
authors.forename: Carlos
authors.initials: C
authors.lastname: Alvarado
authors.forename: Najat C
authors.initials: NC
authors.lastname: Daw
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dome
mesh_terms: D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology
chemical_list: D019772:Topotecan