High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

Introduction: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. Patients and Methods: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1–8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m2 over 3 h, and at a dose of 2 g/m2 per day; continuous infusion was administered on 6 consecutive days (2 g/m2/6 days) every 3 weeks. Results: After a median follow-up of 49 months (range 10–114), median PFS was 2.9 months (range 0.4–9.3) and median overall survival 8.7 months (range 0.4–57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7–7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3–4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. Conclusion: HDI at a total dose of 14 g/m2 with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.