Pazopanib Combined With Vincristine and Irinotecan in Relapsed Wilms Tumor: Encouraging Outcomes in a Heavily Pretreated Pediatric Cohort

BACKGROUND: While Wilms tumor (WT) typically has a favorable prognosis, relapsed cases-especially those with high-risk histology-remain therapeutically challenging after intensive frontline therapy. The combination of vincristine and irinotecan has demonstrated activity in pediatric solid tumors, and pazopanib, a multi-targeted tyrosine kinase inhibitor, might enhance treatment efficacy through antiangiogenic mechanisms. METHODS: This report included six children with relapsed WT treated between 2015 and 2022 at Bambino Gesù Children's Hospital, Rome. All patients had received prior multimodal therapy, including six chemotherapeutic agents. The VIPaz regimen (vincristine, irinotecan, pazopanib) was administered as second- or third-line therapy in combination with surgery and/or radiotherapy. Treatment response and toxicity were evaluated. RESULTS: Five out of six patients (83%) responded to the treatment. Three (50%) achieved complete remission and remained disease-free at 27, 74, and 76 months post-treatment. VIPaz was generally well-tolerated. No Grade >3 toxicities were observed. CONCLUSION: VIPaz in combination with surgery and/or radiotherapy demonstrated an acceptable safety profile and durable responses in 50% of heavily pretreated patients with relapsed high-risk WT. Although limited by small sample size and retrospective design, these findings support further prospective evaluation of pazopanib-based regimens and biomarker-driven approaches in this population.