Epirubicin and Ifosfamide with Preoperative Radiation for High-Risk Soft Tissue Sarcomas

Background: The optimal treatment of high-risk soft tissue sarcomas (STS) of the extremities remains controversial. We report follow-up from a phase II study of dose-intense chemotherapy with preoperative hypofractionated radiation in this population supplemented with subsequent data from an extensive institutional experience using this regimen. Methods: Patients with localized, intermediate- or high-grade STS of the extremity or body wall measuring CloseSPigtSPi 5 cm were treated with epirubicin 30 mg/m ² /day and ifosfamide 2.5 g/m ² /day on days 1–4 every 21 days for 3 preoperative and 3 postoperative cycles. During cycle 2 of preoperative therapy, epirubicin was omitted, and a total of 28 Gy of radiation (8 fractions) was delivered. Twenty-five patients were treated on the phase II study (2002–2005). Fifty-one additional patients were identified from a retrospective chart review (2005–2014). Results: The 5-year rates for overall survival, distant disease-free survival, and freedom from local regional failure were 70.4% (95% CI 59.2–83.7%), 55.9% (95% CI 44.5–70.2%), and 87.2% (95% CI 77.9–96.5%) respectively. Thirty-eight percent of tumors (29/76) demonstrated ≥ 90% pathologic response. Wound complications occurred in 32% (24/76) of patients. Discussion: Treatment with preoperative radiation and pre- and post-operative epirubicin and ifosfamide was associated with favorable clinical outcomes. Survival and recurrence rates were comparable to those reported with other preoperative chemotherapy regimens in high-risk extremity sarcomas. Use of trimodality therapy should be considered for appropriate high-risk STS patients.