Topotecan distribution in an anephric infant with therapy-resistant bilateral Wilms tumor with a novel germline WT1 gene mutation.
The therapeutic strategy for bilateral Wilms tumor (WT) remains a challenge. Especially in cases with chemotherapy resistant disease, bilateral nephrectomy is sometimes inevitable. For optimal cure rates stage V WT patients benefit from adjuvant treatment; however, there are limited data available on chemotherapy pharmacokinetics in anephric children. In this report, we describe a 10-month old girl with bilateral Wilms tumor and a novel germline WT1 gene mutation. This patient hardly showed any response on preoperative chemotherapy, and ultimately, underwent sequential bilateral tumor-nephrectomy. Subsequently, during peritoneal dialysis, she received topotecan as adjuvant chemotherapy based on plasma levels, indicating that this is a reasonable option as adjuvant treatment in therapy-resistant Wilms tumor patients after bilateral nephrectomy. This case showed a novel germline WT1 gene mutation of which the correlation with resistant phenotype has to be confirmed in larger cohorts of WT patients.
Lugtenberg
Rieneke T
RT
Department of Pediatric Hematology/Oncology, Erasmus MC-Sophia Children's Hospital, Room Sp2568, P. O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Cransberg
Karlien
K
Loos
Walter J
WJ
Wagner
Anja
A
Alders
Marielle
M
van den Heuvel-Eibrink
Marry M
MM
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics; D003609:Dactinomycin / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D016162:Genes, Wilms Tumor; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D019656:Loss of Heterozygosity; D008657:Metabolic Clearance Rate; D009392:Nephrectomy; D010530:Peritoneal Dialysis; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019772:Topotecan / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology; D009396:Wilms Tumor / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000601:surgery
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D022821:RNA Splice Sites; D003609:Dactinomycin; D014750:Vincristine; D019772:Topotecan; D004317:Doxorubicin