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

SIMPLE SUMMARY: Ifosfamide is commonly used to treat patients with soft-tissue and bone sarcoma, with greater efficacy observed with higher doses that generally require inpatient treatment and may result in significant myelosuppression and renal toxicity. In the palliative setting, continuous infusional ifosfamide (14 g/m(2)/14 days) is increasingly employed in an attempt to mitigate toxicity, and for ease of administration as an outpatient regimen. This study describes the efficacy and toxicity profile of 14-day continuous infusional ifosfamide in adult and teenage young adult (TYA) patients with relapsed or metastatic soft-tissue and bone sarcoma. ABSTRACT: Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m(2)/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/m(2)/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.