Histologic response of dose‐intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high‐risk soft tissue sarcomas

BACKGROUND. The authors studied a dose‐intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high‐risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis. METHODS. Twenty‐five patients with intermediate‐grade or high‐grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m 2 /day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m 2 /day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). RESULTS. Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty‐one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide‐induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of ≥95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21–59%). Estimates of 2‐year overall and disease‐free survival were 84% (95% CI, 66–100%) and 62% (95% CI, 37–86%), respectively. CONCLUSIONS. A high rate of ≥95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity. Cancer 2008. ©2008 American Cancer Society.