REFINING THERAPEUTIC STRATEGIES FOR PATIENTS WITH RESISTANT WILMS-TUMOR

Purpose: Despite the excellent prognosis for 90% of patients with Wilm s' tumor, survival remains poor among those with recurrent or advanced disease or tumors of unfavorable histology. We sought to identify a c hemotherapy regimen for this subset of patients that offers potential efficacy with minimal nephrotoxicity. Patients and Methods: Through a review of patients' medical records, we compared the efficacy and neph rotoxicity of ifosfamide, cisplatin, cisplatin/etoposide, and ifosfami de/carboplatin/etoposide (ICE) regimens in 32 patients with recurrent (n = 23), refractory (n = 1), or metastatic (n = 8) Wilms' tumor, incl uding six with tumors having unfavorable histologic features. Results: Single-agent ifosfamide was minimally nephrotoxic and induced respons es in three of 11 patients, but none have survived. Cisplatin with or without etoposide induced responses in six of 18 patients with recurre nt Wilms' tumor (there is one long-term survivor). Seven of eight pati ents with newly diagnosed extensive metastatic disease responded to ci splatin/etoposide plus vincristine, dactinomycin, adriamycin, and radi otherapy. This regimen produced three long-term survivors, but was ass ociated with significant nephrotoxicity. The ifosfamide, carboplatin, and etoposide regimen induced responses in four of five patients treat ed, and had minimal nephrotoxicity. Two remain free of disease progres sion 22 months after ocurrence. Conclusions: Although long-term surviv al remains to be determined, the ICE combination appears to be effecti ve against recurrent Wilms' tumor without endangering the patients' si ngle remaining kidney. Myelotoxicity can be ameliorated by administeri ng growth factors. We suggest that ICE chemotherapy be considered for the primary treatment of high-risk patients with Wilms' tumor.