INTRODUCTION
Outcomes for children with advanced stage high-risk renal (HRR) tumors, such as malignant rhabdoid tumors (MRT), diffuse anaplastic Wilms tumors (DAWT), and clear cell sarcoma of the kidney (CCSK), are markedly worse than for favorable histology Wilms Tumor.1-5 Large collaborative group trials, such as Children’s Oncology Group’s (COG) AREN0321, have improved outcomes for some children with HRR tumors using increasingly intensive, multi-agent chemotherapy regimens. Yet for MRT and other INI-1 deficient (INI-) tumors, which can also occur outside the kidney, outcomes remain dismal. Chemotherapy for HRR/INI- tumors typically combines common agents, such as vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide. Prospective studies, including the National Wilms Tumor Study Group studies and COG AREN0321, have omitted ifosfamide from upfront use due to concerns about nephrotoxicity in these patients, many of whom require nephrectomy. Toxicity concerns have also limited therapy intensification strategies that have been successful in other aggressive pediatric malignancies.
Despite prospective trial avoidance of upfront ifosfamide, a few case studies have reported patients with MRT successfully treated using alternating cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) and ifosfamide, carboplatin, and etoposide (ICE). However, ICE-containing therapies can be nephrotoxic and potentially difficult to tolerate in very young children, particularly those who receive a nephrectomy. These tolerability concerns have limited the use of ICE and other ifosfamide-containing regimens in patients with HRR/INI- tumors, despite its use for relapsed renal tumors and other aggressive pediatric solid tumors.9-11 Further analysis is needed to evaluate the effectiveness and tolerability of VDC-ICE as front-line therapy in these children.
Beginning in 2006, our institution implemented a standard treatment plan, alternating cycles of VDC and ICE (hereafter referred to as VDC-ICE), for patients presenting with HRR/INI- tumors and offered it to patients who were not eligible for or refused an open clinical trial at the time of presentation. We now report upon the clinical course, complications, and toxicities experienced by our patients treated with this regimen.