Abstract
Background: 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. Methods: 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/m2/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. Results: 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, p = 0.034) and CR2 (HR 0.126, p < 0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. Conclusions: HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.
Highlights
High-grade osteosarcoma is the most frequent primary bone tumor that usually occurs in children and young adults [1,2]
All patients were pretreated with doxorubicin and cisplatin, while methotrexate
Thirty-two (63%) patients had already been treated with standard dose of ifosfamide for the primary tumor, according to the following schedules: ifosfamide 2 g/m2 /day, day 1–5, 5 day-continuous infusion, Ifosfamide 3 g/m2 /day, day 1–3, or Ifosfamide 2.5 g/m2 /day, day 1–3
Summary
High-grade osteosarcoma is the most frequent primary bone tumor that usually occurs in children and young adults [1,2]. Cells 2020, 9, 2389 methotrexate, +/− ifosfamide) significant improvement in prognosis has been registered with a 5-year survival rate increase from 10% (surgery alone) to nearly 70% (surgery and chemotherapy) in patients with localized disease [3,4,5]. Ifosfamide (or cyclophosphamide) at standard or high dose alone or in combination with etoposide, and gemcitabine/docetaxel, have all been employed for patients with osteosarcoma at the time of recurrence [9,10,11,12,13,14,15,16,17,18] (Table 1). The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. Methods: Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/−.
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