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

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Limited evidence exists for high-dose ifosfamide (HD-IFO) in relapsed osteosarcoma.
• Retrospective analysis of HD-IFO activity in this patient population is warranted.

Purpose of the Study:

• To evaluate the efficacy and outcomes of high-dose ifosfamide in patients with relapsed osteosarcoma.
• To identify factors correlating with treatment response and survival.

Main Methods:

• Retrospective study of 51 relapsed osteosarcoma patients treated with HD-IFO (3 g/m²/day c.i. days 1-5 q21d).
• Response assessed by RECIST1.1 criteria; progression-free survival (PFS), duration of response (DOR), and overall survival (OS) evaluated.
• PARP1 expression and gene mutations analyzed via immunohistochemistry and next-generation sequencing.

Main Results:

• Overall response rate (ORR) was 20% (1 CR, 9 PR). Median DOR was 5 months.
• Median PFS was 6 months, 6-month PFS was 51%, median OS was 15 months, and 2-year OS was 30%.
• Previous ifosfamide use (HR 2.007) correlated with worse PFS, while complete surgical remission (CR2) (HR 0.126) correlated with improved OS. No correlation with PARP1 or gene mutations.

Conclusions:

• High-dose ifosfamide demonstrates significant activity in relapsed osteosarcoma.
• HD-IFO should be considered a standard first-line option for relapsed osteosarcoma and a control arm for future trials.
• Achieving a second complete surgical remission is a critical prognostic factor for survival.