Maintenance DFMO Increases Survival in High Risk Neuroblastoma

Giselle L.Saulnier Sholler; William Ferguson; Genevieve Bergendahl; Jeffrey P. Bond; Kathleen Neville; Don Eslin; Valerie Brown; William Roberts; Randal K. Wada; Javier Oesterheld; Deanna Mitchell; Jessica Foley; Nehal S. Parikh; Francis Eshun; Peter Zage; Jawhar Rawwas; Susan Sencer; Debra Pankiewicz; Monique Quinn; Maria Rich; Joseph Junewick; Jacqueline M. Kraveka

doi:10.1038/s41598-018-32659-w

Maintenance DFMO Increases Survival in High Risk Neuroblastoma

Giselle L.Saulnier Sholler, William Ferguson, Genevieve Bergendahl, Jeffrey P. Bond, Kathleen Neville, Don Eslin, Valerie Brown, William Roberts, Randal K. Wada, Javier Oesterheld, Deanna Mitchell, Jessica Foley, Nehal S. Parikh, Francis Eshun, Peter Zage, Jawhar Rawwas, Susan Sencer, Debra Pankiewicz, Monique Quinn, Maria RichJoseph Junewick, Jacqueline M. Kraveka

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Abstract

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/m² 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.

Original language	English (US)
Article number	14445
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-32659-w
State	Published - Dec 1 2018

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Sholler, G. L. S., Ferguson, W., Bergendahl, G., Bond, J. P., Neville, K., Eslin, D., Brown, V., Roberts, W., Wada, R. K., Oesterheld, J., Mitchell, D., Foley, J., Parikh, N. S., Eshun, F., Zage, P., Rawwas, J., Sencer, S., Pankiewicz, D., Quinn, M., ... Kraveka, J. M. (2018). Maintenance DFMO Increases Survival in High Risk Neuroblastoma. Scientific Reports, 8(1), Article 14445. https://doi.org/10.1038/s41598-018-32659-w

Sholler, GLS, Ferguson, W, Bergendahl, G, Bond, JP, Neville, K, Eslin, D, Brown, V, Roberts, W, Wada, RK, Oesterheld, J, Mitchell, D, Foley, J, Parikh, NS, Eshun, F, Zage, P, Rawwas, J, Sencer, S, Pankiewicz, D, Quinn, M, Rich, M, Junewick, J & Kraveka, JM 2018, 'Maintenance DFMO Increases Survival in High Risk Neuroblastoma', Scientific Reports, vol. 8, no. 1, 14445. https://doi.org/10.1038/s41598-018-32659-w

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abstract = "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/m2 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.",

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AU - Sholler, Giselle L.Saulnier

AU - Ferguson, William

AU - Bergendahl, Genevieve

AU - Bond, Jeffrey P.

AU - Neville, Kathleen

AU - Eslin, Don

AU - Brown, Valerie

AU - Roberts, William

AU - Wada, Randal K.

AU - Oesterheld, Javier

AU - Mitchell, Deanna

AU - Foley, Jessica

AU - Parikh, Nehal S.

AU - Eshun, Francis

AU - Zage, Peter

AU - Rawwas, Jawhar

AU - Sencer, Susan

AU - Pankiewicz, Debra

AU - Quinn, Monique

AU - Rich, Maria

AU - Junewick, Joseph

AU - Kraveka, Jacqueline M.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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/m2 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.

AB - 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/m2 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.

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JF - Scientific Reports

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ER -

Maintenance DFMO Increases Survival in High Risk Neuroblastoma

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