Venetoclax plus cyclophosphamide and topotecan in heavily pre-treated relapsed metastatic neuroblastoma: a single center case series

被引：4

作者：

De Ioris, Maria Antonietta ^{[1
]}

Fabozzi, Francesco ^{[1
]}

Del Bufalo, Francesca ^{[1
]}

Del Baldo, Giada ^{[1
]}

Villani, Maria Felicia ^{[2
]}

Cefalo, Maria Giuseppina ^{[1
]}

Garganese, Maria Carmen ^{[2
]}

Stracuzzi, Alessandra ^{[3
]}

Tangari, Federica ^{[4
]}

Greco, Arturo Maria ^{[4
]}

Giovannoni, Isabella ^{[3
]}

Carta, Roberto ^{[1
]}

D'Andrea, Maria Luisa ^{[5
]}

Mastronuzzi, Angela ^{[1
]}

Locatelli, Franco ^{[1
,6
]}

机构：

[1] Bambino Gesu Pediat Hosp, Dept Pediat Hematol & Oncol & Cell & Gene Therapy, IRCCS, Rome, Italy

[2] Bambino Gesu Pediat Hosp, Nucl Med Unit, IRCCS, Rome, Italy

[3] Bambino Gesu Pediat Hosp, Pathol Unit, IRCCS, Rome, Italy

[4] Bambino Gesu Pediat Hosp, Unit Clin Pharm, IRCCS, Rome, Italy

[5] Bambino Gesu Pediat Hosp, Dept Imaging, IRCCS, Rome, Italy

[6] Univ Cattolica Sacro Cuore, Dept Life Sci & Publ Hlth, Milan, Italy

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

关键词：

REFRACTORY NEUROBLASTOMA; PHASE-II; CHILDREN; BCL-2; COMBINATION; INHIBITION; SURVIVAL;

D O I：

10.1038/s41598-023-44993-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：5

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