The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is dismal, calling for new therapeutic strategies. Venetoclax (VEN) is a highly selective, potent, orally bioavailable, BCL-2 inhibitor small-molecule that showed a synergistic effect with cyclophosphamide and topotecan (Cy-Topo) in murine NB models. Our aim was to evaluate the feasibility of VEN plus Cy-Topo in children with R/R NB. Four patients, who had previously failed > 3 lines of treatment, were treated with VEN plus Cy-Topo based on a 28-day schedule in an outpatient setting. BCL-2 expression in immunochemistry on tumor samples at relapse and the BCL2 gene status was evaluated in all patients. The main toxicity was hematological, with grade 4 neutropenia and thrombocytopenia occurring in all courses and leading to transient VEN discontinuation. Grade 3 oral mucositis was observed in 1/8 courses. No other grade 2-4 toxicities were observed. BCL-2 was expressed in all tumors, while no molecular abnormalities in the BCL-2 genes were detected. A stable disease was observed in all patients, without any progression during the study period. VEN plus Cy-Topo is well tolerated, with encouraging results that may be improved by testing the schedule in less advanced patients.
Venetoclax plus cyclophosphamide and topotecan in heavily pre-treated relapsed metastatic neuroblastoma. A single center case series / Antonietta De Ioris, M., Fabozzi, F., Del Bufalo, F., Del Baldo, G., Felicia Villani, M., Giuseppina Cefalo, M., Carmen Garganese, M., Stracuzzi, A., Tangari, F., Greco, A.M., Giovannoni, I., Carta, R., Luisa D'Andrea, M., Mastronuzzi, A., Locatelli, F.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 13:1(2023). [10.1038/s41598-023-44993-9]
Venetoclax plus cyclophosphamide and topotecan in heavily pre-treated relapsed metastatic neuroblastoma. A single center case series
Francesco Fabozzi;Giada Del Baldo;Alessandra Stracuzzi;Federica Tangari;Arturo Maria Greco;Roberto Carta;Angela Mastronuzzi;
2023
Abstract
The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is dismal, calling for new therapeutic strategies. Venetoclax (VEN) is a highly selective, potent, orally bioavailable, BCL-2 inhibitor small-molecule that showed a synergistic effect with cyclophosphamide and topotecan (Cy-Topo) in murine NB models. Our aim was to evaluate the feasibility of VEN plus Cy-Topo in children with R/R NB. Four patients, who had previously failed > 3 lines of treatment, were treated with VEN plus Cy-Topo based on a 28-day schedule in an outpatient setting. BCL-2 expression in immunochemistry on tumor samples at relapse and the BCL2 gene status was evaluated in all patients. The main toxicity was hematological, with grade 4 neutropenia and thrombocytopenia occurring in all courses and leading to transient VEN discontinuation. Grade 3 oral mucositis was observed in 1/8 courses. No other grade 2-4 toxicities were observed. BCL-2 was expressed in all tumors, while no molecular abnormalities in the BCL-2 genes were detected. A stable disease was observed in all patients, without any progression during the study period. VEN plus Cy-Topo is well tolerated, with encouraging results that may be improved by testing the schedule in less advanced patients.| File | Dimensione | Formato | |
|---|---|---|---|
|
De Ioris_Venetoclax_2023.pdf
accesso aperto
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Creative commons
Dimensione
1.22 MB
Formato
Adobe PDF
|
1.22 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
