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Combination of metronomic cyclophosphamide and dietary intervention for neuroblastoma.

Morscher RJ, Aminzadeh-Gohari S Hauser-Kronberger C, Feichtinger RG, Sperl W, and Kofler B from the Laura Bassi Centre of Expertise-THERAPEP, Department of Pediatrics, Paracelsus Medical University, the Division of Medical Genetics, Medical University Innsbruck, the Department of Pathology, Paracelsus Medical University and the Department of Pediatrics, Paracelsus Medical University in Salzburg, Austria have just pubnlished in Oncotarget a paper entitlted "Combination of metronomic cyclophosphamide and dietary intervention inhibits neuroblastoma growth in a CD1-nu mouse model."

They combined an anti-angiogenic approach with metronomic cyclophophomide with diet intervention to target NB metabolism in both nmyc amplified and non nmyc amplifeid models. Metronomic cyclophosphamide (MCP) monotherapy significantly inhibited NB growth and prolonged host survival. Growth inhibition was more pronounced in MYCN-amplified xenografts. Immunohistochemical evaluation of this subtype showed significant decrease in blood vessel density and intratumoral hemorrhage accompanied by blood vessel maturation and perivascular fibrosis. Up-regulation of VEGFA was not sufficient to compensate for the effects of the MCP regimen. Reduced Bcl-2 expression and increased caspase-3 cleavage were evident. In contrast non MYCN-amplified tumors developed resistance, which was accompanied by Bcl-2-up-regulation. Combining MCP with a ketogenic diet and/or calorie-restriction significantly enhanced the anti-tumor effect. Calorie-restricted ketogenic diet in combination with MCP resulted in tumor regression in all cases.

They therefore show an increased efficacy when combining an anti-angiogenic cyclophosphamide dosing regimen with dietary intervention in a preclinical NB model.

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