High-dose ifosfamide as second- or third-line chemotherapy in refractory bone and soft tissue sarcoma patients

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.

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/m(2) over 3 h, and at a dose of 2 g/m(2) per day; continuous infusion was administered on 6 consecutive days (2 g/m(2)/6 days) every 3 weeks.

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.

HDI at a total dose of 14 g/m(2) with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.