5513 Background: The combination of paclitaxel and carboplatin is the most widely used chemotherapy regimen for patients (pts) with advanced ovarian cancer, producing a median survival of approximately 36 months. Recently, the addition of bevacizumab, an angiogenesis inhibitor, has improved progression-free survival (PFS) when compared to paclitaxel/carboplatin alone. Sorafenib is an oral multi-kinase inhibitor with effects on tumor angiogenesis through inhibition of the VEGF receptor. The purpose of this randomized phase II study was to compare efficacy of paclitaxel/carboplatin with and without sorafenib. Methods: Women with histologically confirmed, maximally debulked, previously untreated stage III/IV epithelial ovarian carcinoma were randomized to receive paclitaxel 175 mg/m2and carboplatin AUC 6 (PC) or PC + sorafenib 400 mg PO BID (S). All patients received 6 cycles, given every 3 weeks; pts receiving PC+S continued single agent sorafenib for 52 weeks total. The primary endpoint was 2-year PFS rate. Results: 85 pts were randomized between 1/07 and 10/11 (PC+S 43; PC 42). Pt characteristics were similar between groups, except that more patients with only CA125 elevation received PC+S (65% vs 43%). Overall, 67 pts (79%) completed 6 cycles of chemotherapy (PC+S 74%; PC 83%). More patients stopped PC+S due to toxicity (14% vs 7%). 22 pts (51%) receiving PC+S began single agent S after 6 cycles PC, and 12 pts (28%) completed 52 weeks of S. There was no difference in the 2-year PFS rates: PC+S 40%, PC 39%. Overall survival comparisons were also similar (p = 0.36). Pts receiving PC+S had more grade 3 rash (33% vs 0%) and hand-foot syndrome (9% vs 0%). Conclusions: The addition of sorafenib did not improve the efficacy of standard first-line PC in pts with stage III/IV ovarian carcinoma, and resulted in additional toxicity. Clinical trial information: NCT00390611.
A randomized phase II study of BB-10010: a variant of human macrophage inflammatory protein-1α for patients receiving high-dose etoposide and cyclophosphamide for malignant lymphoma and breast cancer
