Document Type
Article
Publication Date
9-1-2023
Identifier
DOI: 10.1002/ijc.34569
Abstract
Children with relapsed/refractory (R/R) neuroblastoma (NB) and medulloblastoma (MB) have poor outcomes. We evaluated the efficacy of nifurtimox (Nfx) in a clinical trial for children with R/R NB and MB. Subjects were divided into three strata: first relapse NB, multiply R/R NB, and R/R MB. All patients received Nfx (30 mg/kg/day divided TID daily), Topotecan (0.75 mg/m2 /dose, days 1-5) and Cyclophosphamide (250 mg/m2 /dose, days 1-5) every 3 weeks. Response was assessed after every two courses using International Neuroblastoma Response Criteria and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. One hundred and twelve eligible patients were enrolled with 110 evaluable for safety and 76 evaluable for response. In stratum 1, there was a 53.9% response rate (CR + PR), and a 69.3% total benefit rate (CR + PR + SD), with an average time on therapy of 165.2 days. In stratum 2, there was a 16.3% response rate, and a 72.1% total benefit rate, and an average time on study of 158.4 days. In stratum 3, there was a 20% response rate and a 65% total benefit rate, an average time on therapy of 105.0 days. The most common side effects included bone marrow suppression and reversible neurologic complications. The combination of Nfx, topotecan and cyclophosphamide was tolerated, and the objective response rate plus SD of 69.8% in these heavily pretreated populations suggests that this combination is an effective option for patients with R/R NB and MB. Although few objective responses were observed, the high percentage of stabilization of disease and prolonged response rate in patients with multiply relapsed disease shows this combination therapy warrants further testing.
Journal Title
International journal of cancer. Journal international du cancer
Volume
153
Issue
5
First Page
1026
Last Page
1034
MeSH Keywords
Child; Humans; Topotecan; Nifurtimox; Medulloblastoma; Neoplasm Recurrence, Local; Neuroblastoma; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Cerebellar Neoplasms
Keywords
medulloblastoma; neuroblastoma; nifurtimox
Recommended Citation
Eslin D, Zage PE, Bergendahl G, et al. A phase II trial of nifurtimox combined with topotecan and cyclophosphamide for refractory or relapsed neuroblastoma and medulloblastoma. Int J Cancer. 2023;153(5):1026-1034. doi:10.1002/ijc.34569
Comments
Grant support
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Publisher's Link: https://onlinelibrary.wiley.com/doi/10.1002/ijc.34569