This trial compared the efficacy and toxicity of standard first-line treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma. Patients with stage 3 or 4 epithelial ovarian cancer with residual measurable disease or elevated CA-125 levels after maximal surgical cytoreduction were randomized (1:1) to receive treatment with paclitaxel (175 mg/m2, 3 h infusion, day 1) and carboplatin (AUC 6.0, IV, day 1) with or without sorafenib 400 mg orally twice daily (PO BID). Patients were reevaluated for response after completing 6 weeks of treatment (two cycles); responding or stable patients received six cycles of paclitaxel/carboplatin. Patients receiving the sorafenib-containing regimen continued sorafenib (400 PO BID) for a total of 52 weeks. Eighty-five patients were randomized and received treatment.Efficacy was similar for patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin: overall response rates 69% versus 74%; median progression-free survival 15.4 versus 16.3 months; 2 year survival 76% versus 81%. The addition of sorafenib added substantially to the toxicity of the regimen; rash, hand–foot syndrome, mucositis, and hypertension were significantly more common in patients treated with sorafenib. The addition of sorafenib to standard paclitaxel/carboplatin did not improve efficacy and substantially increased toxicity in the first-line treatment of advanced epithelial ovarian cancer. Based on evidence from this study and other completed trials, sorafenib is unlikely to have a role in the treatment of ovarian cancer.

Bromodeoxyuridine (BrdU) was administered to 128 newly diagnosed patients with standard risk acute myelocytic leukaemia (AML) for cell cycle measurements. Labelling indices (LI) were obtained from both the bone marrow aspirate (BMasp) and biopsies (bx) and durations of S-phase (Ts) and total cell cycle time (Tc) were measured by double-labelling the S-phase cells in vitro with tritiated thymidine. Median LI BMasp was 8% and from BMbx was 25%. The median Ts was 12 h (range 3.1-35 h) and Tc was 48 h (range 11.5-211 h). All patients received induction therapy with a combination of cytosine arabinoside and an anthracycline. Outcome of therapy or FAB type were not related to cell cycle characteristics. Patients with above median LI BMasp, however, had longer remission durations (P = 0.03) as did patients with above median Ts (P = 0.03) and Tc (P = 0.03). Upon longer follow-ups, even some of the patients with slowly cycling myeloblasts have relapsed (log rank P = 0.453 and 0.203 for Ts and Tc respectively). We conclude that patients with rapidly cycling cells tend to relapse faster; however, slowly cycling nature of myeloblasts is not associated with curability.

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.

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