Abstract views : 215 ; PDF downloads : 61

Main Article Content

Paolo Indolfi, MD, Selim Corbacioglu, MD, Silverio Perrotta, MD, Francesca Rossi, MD, Antonio Marte, MD, Elvira Pota, MD, Martina Di Martino, MD, Daniela Di Pinto, MD, Cristiana Indolfi, MD, Fiorina Casale, MD


The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge, and currently there are no known curative salvage regimens. In this paper we investigated the effect of imatinib with rapamycin and the chemotherapeutic agents temozolomide and irinotecan. We treated two children with recurrent neuroblastoma with this so called RIST protocol. Both patients, off therapy for 15 and 31 months, respectively are well, and developing normally, without any complications. These findings suggest that a combination regimen of RIST may provide a therapeutic benefit with a favorable toxicity profile to a unfortunate subset of patients with neuroblastoma.

Article Details

How to Cite
INDOLFI, Paolo et al. Targeted molecular therapy (modified RIST regimen) in relapsed high risk stage IV neuroblastoma: two cases report. Theory and Clinical Practice in Pediatrics, [S.l.], v. 2, n. 1, jan. 2018. ISSN 2529-749X. Available at: <http://journals.syncsci.com/index.php/TCPP/article/view/73>. Date accessed: 20 mar. 2018. doi: https://doi.org/10.25082/TCPP.2018.01.002.
Case Study


1. Pourquier P, Waltman JL, Urasaki Y, et al. Topoisomerase-I-mediated cytotoxicity of N-methyl-N- mitro-N-mitrosoguanide: trapping of topoisomerase I by the O6- methylguanine Cancer Res 2001; 61:53-58
2. Reardon DA, Quinn JA, Rich JN, et al. Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma. Cancer 2005; 104: 1478-1486
3. Corbacioglu S, Kilic M, Westhoff MA, et al. Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces ligand independent growth and is responsive to a synergistic effects of imatinib and rapamycin. Blood 2006; 108: 3504-3513
4. Corbacioglu S, Steinbach D, Lode HN, et al. The RIST design: a molecularly targeted multimodal approach for the treatment of patients with relapsed and refractory neuroblastoma. J Clin Oncol 2013; 31 (suppl; abstr 10017)
5. Wagner LM, Crews KR, Iacono LC, et al. Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors. Clin Cancer Res 2004; 10: 840-848
6. Nicholson HS, Krailo M, Ames MM, et al. Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group. J Clin Oncol 1998; 16: 3037-3043
7. Estlin EJ, Lashford L, Ablett S, et al. Phase I study of temozolomide in pediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group. Br J Cancer 1998; 78: 652-661
8. De Sio L, Milano GM, Castellano A, et al. Temozolomide in resistant or relapsed pediatric solid tumors. Pediatr Blood Cancer 2006; 47: 30-36
9. Middlemas DS, Stewart CF, Kirstein MN, et al. Biochemical correlates of temozolomide sensitivity in pediatric solid tumor xenograft models. Clin Cancer Res 2000; 6; 998-1007
10. Houghton PJ, Stewart CF, Cheshire PJ, et al. Antitumor activity of temozolomide combined with irinotecan is partly independent of 06- methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Clin Cancer Res 2000; 6: 4110-4118
11. Mixon BA, Eckirich MJ, Lowas S, et al. Vincristine, Irinotecan, and Temozolomide for treatment of relapsed alveolar rhabdomyosarcoma. J Pediatr Hematol Oncol 2013; 35: 163-166
12. Beppu K, Jaboine J, Merchant MS, et al. Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular endothelial growth factor expression. J Natl Cancer Inst 2004; 96: 46-55
13. Vitale R, Cesi V, Nicotra MR, et al. c-KIT is preferentially expressed in MYCN-amplified neuroblastoma and its effect on cell proliferation is inhibited in vitro by STI-571. Int J Cancer 2003; 106: 147-152
14. Heimberg AB, Wang E, McGary EC, et al. Mechanisms of action of rapamycin in gliomas. Neuro Oncol 2005; 7: 1-11
15. Qayum N, Im J, Stratford MR, et al. Modulation of the tumor microvasculature by phosphoinositide-3 kinase inhibition increases doxorubicin delivery in vivo. Clin cancer Res 2012; 18: 161-169
16. Saito K, Matsumoto S, Yasui H, et al. Longitudinal imaging studies of tumor microenvironment in mice treated with the mTOR inhibitor rapamycin Plos One 2012; 7: e49456