Maintenance DFMO Increases Survival in High Risk Neuroblastoma

被引：84

作者：

Sholler, Giselle L. Saulnier ^{[1
,2
]}

Ferguson, William ^{[3
]}

Bergendahl, Genevieve ^{[1
]}

Bond, Jeffrey P. ^{[1
]}

Neville, Kathleen ^{[4
]}

Eslin, Don ^{[5
]}

Brown, Valerie ^{[6
]}

Roberts, William ^{[7
,8
]}

Wada, Randal K. ^{[9
]}

Oesterheld, Javier ^{[10
]}

Mitchell, Deanna ^{[1
]}

Foley, Jessica ^{[1
]}

Parikh, Nehal S. ^{[11
]}

Eshun, Francis ^{[12
]}

Zage, Peter ^{[7
,8
]}

Rawwas, Jawhar ^{[13
]}

Sencer, Susan ^{[13
]}

Pankiewicz, Debra ^{[1
]}

Quinn, Monique ^{[1
]}

Rich, Maria ^{[1
]}

Junewick, Joseph ^{[1
]}

Kraveka, Jacqueline M. ^{[14
]}

机构：

[1] Helen DeVos Childrens Hosp Spectrum Hlth, Grand Rapids, MI 49503 USA

[2] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA

[3] St Louis Univ, Sch Med, St Louis, MO USA

[4] Arkansas Childrens Hosp, 800 Marshall St, Little Rock, AR 72202 USA

[5] Arnold Palmer Hosp Children, Orlando, FL USA

[6] Penn State Milton S Hershey Med Ctr, Penn State Hlth Childrens Hosp, Hershey, PA USA

[7] Rady Childrens Hosp San Diego, San Diego, CA USA

[8] UC San Diego Sch Med, San Diego, CA USA

[9] Kapiolani Med Ctr Women & Children, Honolulu, HI USA

[10] Levine Childrens Hosp, Charlotte, NC USA

[11] Connecticut Childrens Med Ctr, Hartford, CT USA

[12] Phoenix Childrens Hosp, Phoenix, AZ USA

[13] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA

[14] Med Univ South Carolina, Charleston, SC 29425 USA

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

PHASE-I TRIAL; ORNITHINE-DECARBOXYLASE; ALPHA-DIFLUOROMETHYLORNITHINE; CONSOLIDATION TREATMENT; CANCER; MYCN; CLASSIFICATION; POLYMORPHISM; P27(KIP1); ANTIBODY;

D O I：

10.1038/s41598-018-32659-w

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：

High risk neuroblastoma (HRNB) accounts for 15% of all pediatric cancer deaths. Despite aggressive therapy approximately half of patients will relapse, typically with only transient responses to second-line therapy. This study evaluated the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) as maintenance therapy to prevent relapse following completion of standard therapy (Stratum 1) or after salvage therapy for relapsed/refractory disease (Stratum 2). This Phase II single agent, single arm multicenter study enrolled from June 2012 to February 2016. Subjects received 2 years of oral DFMO (750 +/- 250 mg/m(2) twice daily). Event free survival (EFS) and overall survival (OS) were determined on an intention-to-treat (ITT) basis. 101 subjects enrolled on Stratum 1 and 100 were eligible for ITT analysis; two-year EFS was 84% (+/- 4%) and OS 97% (+/- 2%). 39 subjects enrolled on Stratum 2, with a two-year EFS of 54% (+/- 8%) and OS 84% (+/- 6%). DFMO was well tolerated. The median survival time is not yet defined for either stratum. DFMO maintenance therapy for HRNB in remission is safe and associated with high EFS and OS. Targeting ODC represents a novel therapeutic mechanism that may provide a new strategy for preventing relapse in children with HRNB.

引用

页数：9

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