Introduction: Systemic treatment for metastatic soft tissue sarcoma (STS) results in modest activity in second and further lines. The aim of this study was to evaluate the efficacy of ifosfamide and etoposide (IE) as a salvage regimen for patients with metastatic STS.

Methods: A retrospective, single centre study included patients with STS treated with IE from 2010 to 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints were toxicity, response rate (RR) and overall survival (OS). Survival was estimated by the Kaplan–Meier method and log-rank test used to compare the groups.

Results: A total of 33 patients were identified, median age was 43 years, 60% were female, 12 had leiomyosarcoma. IE was used in second line in 51.5% and in >third line in 30.3% of patients. Median number of cycles was four and treatment discontinuation due to grade 3/4 toxicity occurred in 30.3%. The objective RR was 9% and the disease control rate was 60.6%. Median PFS was 4 months (95% CI, 2.1–5.9) and the median OS was 15 months (95% CI, 7.1–22.9). In the univariate analysis, smoking history, line of therapy and prior response to previous chemotherapy were prognostic factors for PFS.

Conclusion: IE showed activity in previously treated STS, but with a non-negligible toxicity profile, worse than that with other available therapies. The use of the IE combination is not supported by our findings outside a clinical trial for soft part sarcomas.