Topotecan is active against Wilms' tumor: results of a multi-institutional phase II study.
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.
Metzger
Monika L
ML
St Jude Children's Research Hospital, Memphis, TN, USA.
Stewart
Clinton F
CF
Freeman
Burgess B
BB
Billups
Catherine A
CA
Hoffer
Fredric A
FA
Wu
Jianrong
J
Coppes
Max J
MJ
Grant
Ronald
R
Chintagumpala
Murali
M
Mullen
Elizabeth A
EA
Alvarado
Carlos
C
Daw
Najat C
NC
Dome
Jeffrey S
JS
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
D019772:Topotecan