Refining therapeutic strategies for patients with resistant Wilm's tumor.

Abstract

Purpose: Despite the excellent prognosis for 90% of patients with Wilms' tumor, survival remains poor among those with recurrent or advanced disease or tumors of unfavorable histology. We sought to identify a chemotherapy 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 nephrotoxicity of ifosfamide, cisplatin, cisplatin/etoposide, and ifosfamide/carboplatin/etoposide (ICE) regimens in 32 patients with recurrent (n = 23), refractory (n = 1), or metastatic (n = 8) Wilms' tumor, including six with tumors having unfavorable histologic features.

Results: Single-agent ifosfamide was minimally nephrotoxic and induced responses in three of 11 patients, but none have survived. Cisplatin with or without etoposide induced responses in six of 18 patients with recurrent Wilms' tumor (there is one long-term survivor). Seven of eight patients with newly diagnosed extensive metastatic disease responded to cisplatin/etoposide plus vincristine, dactinomycin, adriamycin, and radiotherapy. This regimen produced three long-term survivors, but was associated with significant nephrotoxicity. The ifosfamide, carboplatin, and etoposide regimen induced responses in four of five patients treated, and had minimal nephrotoxicity. Two remain free of disease progression 22 months after recurrence.

Conclusions: Although long-term survival remains to be determined, the ICE combination appears to be effective against recurrent Wilms' tumor without endangering the patients' single remaining kidney. Myelotoxicity can be ameliorated by administering growth factors. We suggest that ICE chemotherapy be considered for the primary treatment of high-risk patients with Wilms' tumor.