Real-World Experience of Efficacy and Tolerability of Continuous Infusion Ifosfamide for Advanced Soft Tissue and Bone Sarcoma Patients: A Single Centre Retrospective Cohort

Background In the absence of randomized trials, selecting second or later-line therapies in advanced sarcoma generally hinges on histology, patient performance status, and toxicity profile. We herein report a real-world sarcoma referral center experience on continuous infusion Ifosfamide (ciIFO), in advanced Soft tissue sarcomas (STS) and bone sarcomas (BS) patients, assessing both efficacy and toxicity profile.Methods We retrospectively collected data of STS and BS patients treated with ciIFO (14 g/m2 as a 14-day continuous infusion every 4 weeks) at our Institute from January 2013 to April 2023. The analysis included patients' demographic and clinical characteristics, pathology details, treatment history, radiological response rates (RR), and toxicities per Common Terminology Criteria for Adverse Events (CTCAE) v5.Results Ninety eight patients were included in the analysis. Median age at diagnosis was 49 years, 61% had previously received ifosfamide (IFO) and 83% anthracycline in earlier lines of treatment. Disease control rate (DCR) was 32%, with 9 PR and 22 stable disease (SD). Synovial sarcomas had the best (DCR) (60%). No statistically significant differences in DCR were seen according to sex, previous exposure to ifosfamide-based CT, or ciIFO treatment line. mPFS was 3.0 months; mOS was 11.2 months. ciIFO was well tolerated, with an 11% discontinuation rate and no severe renal toxicity observed.Conclusions ciIFO showed activity across different lines of therapy, achieving a DCR of 32%, and appeared better tolerated than standard-dose IFO regimens, even in a cohort of heavily pretreated patients (18% had an Eastern Cooperative Oncology Group performance status (ECOG PS) >= 2). Synovial and bone sarcoma patients derived the greatest benefit (6-month PFS of 45% in both groups).