High Dose Ifosfamide in Relapsed and Unresectable High-Grade Osteosarcoma Patients: A Retrospective Series.

Emanuela Palmerini, Elisabetta Setola, Giovanni Grignani, Lorenzo D'Ambrosio, Alessandro Comandone, Alberto Righi, Alessandra Longhi, Marilena Cesari, Anna Paioli, Rossella Hakim, Michela Pierini, Emanuela Marchesi, Daniel Vanel, Ymera Pignochino, Davide Maria Donati, Piero Picci, Stefano Ferrari

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Abstract

: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. : Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/- ifosfamide (MAP+/-I)] with measurable disease according to RECIST1.1 were eligible to ifosfamide (3 g/m /day) continuous infusion (c.i.) days 1-5 q21d. RECIST1.1 overall response rate (ORR) (complete response (CR) + partial response (PR)), progression-free survival at 6-month (6m-PFS), duration of response (DOR), and 2-year overall survival (2y-OS) were assessed. PARP1 expression and gene mutations were tested by immunohistochemistry and next-generation sequencing. : 51 patients were included. ORR was 20% (1 CR + 9 PR). Median DOR was 5 months (95%CI 2-7). Median PFS, 6m-PFS, OS, and 2y-OS were 6 months (95%CI 4-9), 51%, 15 months (10-19), and 30%, respectively. A second surgical complete remission (CR2) was achieved in 26 (51%) patients. After multivariate analysis, previous use of ifosfamide (HR 2.007, = 0.034) and CR2 (HR 0.126, <0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. : HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.
Original languageUndefined/Unknown
JournalCells
Volume9
DOIs
Publication statusPublished - Oct 31 2020

Keywords

  • PARP1
  • chemotherapy
  • high-grade bone sarcoma
  • ifosfamide
  • osteosarcoma
  • pediatric bone tumors
  • sequencing

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