Efficacy, safety, and pharmacokinetics of eribulin as monotherapy or in combination with irinotecan for patients with pediatric rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, or Ewing sarcoma

被引：0

作者：

Casanova, M.

Albert, C. M. ^{[2
,3
]}

Bautista, F. ^{[4
,21
]}

Borinstein, S. C. ^{[5
]}

Bradfield, S. ^{[6
]}

Bukowinski, A. ^{[7
]}

Campbell-Hewson, Q. ^{[8
]}

Hawkins, D. S. ^{[2
,3
]}

Kim, A. ^{[9
]}

Milano, G. M. ^{[10
]}

Marshall, L. V. ^{[11
,12
,13
]}

Pinto, N. ^{[14
]}

Pratilas, C. A. ^{[15
]}

Rubio-San-Simon, A. ^{[2
,16
]}

Windsor, R. ^{[17
]}

Majid, O. ^{[18
]}

Scott, R. ^{[18
]}

Jia, Y. ^{[19
]}

Paoletti, C.

Kontny, U. ^{[1
,20
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori, Pediat Oncol Unit, Milan, Italy

[2] Seattle Childrens Hosp, Div Hematol Oncol Bone Marrow Transplant & Cellula, Seattle, WA USA

[3] Univ Washington, Sch Med, Seattle, WA USA

[4] Hosp Nino Jesus, Madrid, Spain

[5] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN USA

[6] Nemours Childrens Hlth, Div Pediat Hematol Oncol, Jacksonville, FL 32207 USA

[7] UPMC Childrens Hosp Pittsburgh, Dept Pediat Hematol Oncol, Pittsburgh, PA USA

[8] Great North Childrens Hosp, Royal Victoria Infirm, Newcastle Upon Tyne, England

[9] Great North Childrens Hosp, Royal Victoria Infirm, Newcastle Upon Tyne, DC, England

[10] IRCCS Osped Pediat Bambino Gesu, Ctr Canc & Blood Disorders, Washington, DE USA

[11] Royal Marsden Hosp, Children & Young Peoples Unit, London, England

[12] Inst Canc Res, Div Clin Studies, London, England

[13] Inst Canc Res, Div Canc Therapeut, London, England

[14] Inst Canc Res, London, CO USA

[15] Johns Hopkins Univ, Sch Med, Aurora, South Africa

[16] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[17] Univ Coll London Hosp NHS Fdn Trust, Children & Young Peoples Canc Serv, London, England

[18] Eisai Ltd, Hatfield, England

[19] Eisai Inc, Nutley, NJ USA

[20] Univ Hosp Aachen, Div Pediat Hematol Oncol & Stem Cell Transplantat, Aachen, Germany

[21] Princess Maxima Ctr Pediat Canc, Utrecht, Netherlands

来源：

ESMO OPEN | 2025年 / 10卷 / 02期

关键词：

soft tissue sarcoma; Ewing sarcoma; pediatric; eribulin; pharmacokinetics; TEMOZOLOMIDE; CHILDREN; PHASE-2;

D O I：

10.1016/j.esmoop.2024.104129

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: In this report, we present results from studies of eribulin as monotherapy (Study 223) and in combination with irinotecan (the phase II part of Study 213) for patients with relapsed/refractory pediatric rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), or Ewing sarcoma (EWS). Patients and methods: Studies 223 and 213 were phase II multicenter trials that enrolled pediatric patients with histologically confirmed disease. Treatment comprised 21-day cycles of eribulin mesylate 1.4 mg/m(2) on days 1 and 8 (Study 223) or eribulin 1.4 mg/m(2) on days 1 and 8 plus irinotecan 40 mg/m(2) on days 1-5 (Study 213). For both studies, the primary endpoints were objective response rate (ORR) and duration of response (DOR); secondary endpoint included safety. Results: In Study 223, 21 patients (RMS, n = 8; NRSTS, n = 8; EWS, n = 5) were enrolled and treated. No responses were observed, resulting in early termination of enrollment. By the data cut-off date (22 February 2021), six patients (RMS, n = 3; NRSTS, n = 1; EWS, n = 2) had stable disease for >5 weeks. All patients had one or more treatmentemergent adverse event (TEAE), most commonly neutrophil count decreased (71.4%). In Study 213 (phase II part), 27 patients (RMS, n = 9; NRSTS, n = 9; EWS, n = 9) were enrolled/treated. By the data cut-off date (9 July 2021), three patients (one in each cohort) had had a response, resulting in an ORR of 11.1% and DORs of 2.9 (RMS), 1.4 (NRSTS), and 15.4 (EWS) months. All patients had one or more TEAE, most commonly diarrhea and neutrophil count decreased (51.9% each). Conclusions: Eribulin, as monotherapy or combination therapy, exhibited a safety profile consistent with that observed previously in adult populations; however, efficacy in both studies was not considered adequate to advance investigation in these disease areas.

引用

页数：8

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