Phase I study of neoadjuvant chemoradiation (CRT) plus sorafenib (S) for high-risk extremity soft tissue sarcomas (STS).

10011^ Background: We previously reported a regimen of epirubicin/ifosfamide (E/I) and hypofractionated radiation (RT) followed by surgery and postoperative E/I. We hypothesize that S + CRT is safe and augments activity through anti-angiogenic mechanisms. We performed dynamic contrast-enhanced MRI using shutter speed pharmacokinetic analysis (SSM DCE-MRI) to assess preoperative therapy effect. Methods: Subjects with >5 cm, grade 2-3 extremity STS were treated in cohorts of escalating S dose using a 3+3 design based on dose-limiting toxicity (DLT) during the first 8 weeks. Daily S was initiated 14 days prior to E/I (E 30 mg/m2/day days 1-3 and I 2.5 g/m2/day days 1-3 every 21 days for 3 pre- and 3 postoperative cycles). 28 Gy preoperative RT was administered in 8 fractions during cycle 2 (E omitted). Primary objective was to determine maximum tolerated dose (MTD). DCE-MRI was performed at baseline, after 2 weeks S, and prior to surgery. Results: 16 subjects were enrolled. Histologies included pleomorphic (...