Continuous 14 Day Infusional Ifosfamide for Management of Soft-Tissue and Bone Sarcoma: A Single Centre Retrospective Cohort Analysis

Abstract

Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m²/cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m²/14d) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated-46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1-24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care.

Keywords: bone sarcoma; chemotherapy; infusional ifosfamide; soft-tissue sarcoma.

Figure 1

Kaplan–Meier (KM) curves showing PFS (left) and OS (right) for all 80 patients—46 patients with STS and 34 with BS. Median PFS was 3.4 months and median OS was 11.8 months.

Figure 2

Kaplan–Meier (KM) curves showing PFS and OS in patients with STS. (A) All STS patients; (B) compared by histological subtype; (C) compared by prior ifosfamide exposure; (D) compared based on the number of previous chemotherapy lines. Median progression-free survival (mPFS) and overall survival (mOS) for each subgroup are shown. SS = synovial sarcoma, LPS = liposarcoma. Statistical analysis was performed using log-rank (Mantel–Cox) test to compare survival curves. * Statistically significant difference between KM curves.

Figure 3

Swimmer plot of STS cohort demonstrating PFS, timing of treatment cessation, and patient status at the time of analysis. Patients 1–15 represent those with synovial sarcoma, patients 16–28 represent those with liposarcoma, whilst patients 19–46 represent those with other STS subtypes.

Figure 4

Kaplan–Meier (KM) curves showing PFS and OS in patients with BS. (A) All BS patients; (B) compared by histological subtype; (C) compared by prior ifosfamide exposure; (D) compared based on the number of previous chemotherapy lines. Median progression-free survival (mPFS) and overall survival (mOS) for each subgroup are shown. ES = Ewing sarcoma. Statistical analysis was performed using log-rank (Mantel–Cox) test to compare survival curves.

Figure 5

Swimmer plot of BS cohort demonstrating PFS and timing of treatment termination, along with details of their current status at the time of analysis.