We previously reported a phase I trial of S added to epirubicin (Epi) and ifosfamide (Ifos) with pre-op radiation (XRT) for patients (pts) with high-risk extremity STS. To further evaluate this regimen, we performed a phase II trial using a primary endpoint of pathologic necrosis rate at time of surgery.
Eligibility: >5 cm, grade 2-3, extremity / body wall STS, limb-sparing candidates. Pts with metastases (mets) who were planned for resection of primary tumor were allowed. Chemotherapy: Epi 30 mg/m2/day D1-3, Ifos 2.5 g/m2/day D1-3 with mesna and pegfilgrastim repeated every 21 days for 3 pre- and 3 post-op cycles. S 400 mg/day was initiated 14 days prior to chemotherapy and continued throughout treatment. XRT: 28 Gy in 8 fractions during cycle 2 (Epi omitted) with a post-op boost for positive margins. Dynamic contrast-enhanced (DCE-) MRI was performed to assess changes in tumor size, perfusion and permeability.
20 pts were enrolled. Median age: 54 (21-68); location: lower extremity (17), upper extremity (3); median size: 13 cm (5-30); histology: pleomorphic/NOS (11), liposarcoma (3), myxofibrosarcoma (3); synovial (2), MPNST (1). 4 pts had mets at baseline. Limb-sparing surgery was performed in all pts. Margins were positive in 4 pts (20%). Most common grade 3-4 toxicities were neutropenia (17 pts), hypophosphatemia (14), thrombocytopenia (13), anemia (13), neutropenic fever/infections (12), other infections (8), hypokalemia (6), encephalopathy (3). 10 pts (50%) had post-op wound complications requiring surgical intervention. 75% of pts completed pre-op therapy, but only 20% completed all post-op therapy. 8 tumors (40%) demonstrated ≥ 90% necrosis at surgery. There were 2 partial responses among 4 pts with mets. With a median follow-up of 27 months (10-43) among 16 pts with localized disease, 50% have developed mets. There have been no local recurrences.
While substantial tumor necrosis was achieved with this regimen, there was a high rate of distant relapse which may be influenced by small sample size. Wound complications were frequent but recoverable and side effects were similar to previously reported. Results of DCE-MRI analysis will be presented at meeting.
Clinical trial identification
Legal entity responsible for the study
Christopher W. Ryan, M.D.
Bayer (drug only).
C.W. Ryan: Drug-only support for the conduct of this study: Bayer. W. Huang: Financial interest: Imbio, LLC (a company that may have a commercial interest in the results of this research and technology). This potential individual and institutional conflict of interest has been reviewed and managed by OHSU. All other authors have declared no conflicts of interest.