J Clin Oncol

J Clin Oncol. hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased ( .0001); soluble VEGF receptor-2 ( .0001) and CECs (= .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (= .04) and the 16W-DCR (= .02), respectively. (S)-Willardiine Lower interleukin (IL)-8 levels at baseline (= .01) and throughout treatment ( .04) (S)-Willardiine were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. Retn .001) [14]. For CAF measurements, whole blood (10 mL) was collected in heparin tubes. Plasma levels of matrix metalloproteinase (MMP)-2, MMP-9, VEGF-A, soluble VEGFR-2 (sVEGFR-2), interleukin (IL)-6, IL-8, placental growth factor (PlGF), stromal derived factor (SDF)-1, and tumor necrosis factor (TNF)- were decided using commercial enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN). Plasma samples were assayed in duplicate. Optical density values were considered significant if found to be at least twice as high as the background noise. Statistical Analysis Patients were enrolled using a two-stage Fleming design [15]. In stage 1, 25 patients had to be treated with bevacizumab at a dose of 5 mg/kg. If disease control at 16 weeks was observed in 11 patients, enrollment at that dose had to be stopped and 25 further patients had to be enrolled within stage 2 and treated with bevacizumab at a dose of 10 mg/kg. Otherwise, the next 25 patients enrolled in stage 2 were planned to receive 5 mg/kg bevacizumab. Thus, a maximum of 50 patients had to be included in two actions, giving a power of 0.96 (96% chance of demonstrating efficacy if the 16W-DCR was 65%). The risk (one sided) was 0.03 (3% chance of demonstrating efficacy if the 16W-DCR was 40%). Safety and activity analyses included all patients receiving at least one dose of bevacizumab. The 16W-DCR and ORR were reported with their 95% confidence intervals (CIs). PFS and OS curves were calculated using the KaplanCMeier method. Nonparametric assessments (Wilcoxon or KruskalCWallis assessments as appropriate) were used to compare biomarker values at (S)-Willardiine baseline, day 3, day 15, and day 60, as well as changes from baseline to day, day 15, and day 60, according to patient prognostic characteristics (WHO PS score, Barcelona Clinic Liver Cancer [BCLC] classification [2], and CLIP score) and outcome (16W-DCR, ORR, and PFS and OS times). The log-rank test was used to compare survival curves. The trial is usually registered in ClinicalTrials.gov (identifier, “type”:”clinical-trial”,”attrs”:”text”:”NCT00162669″,”term_id”:”NCT00162669″NCT00162669). Role of the Funding Source The funding source had no role in the initiation and design of the study, data collection, analysis, and interpretation, writing of the report, or the decision to submit for publication. The funding source did not have access to the raw data. The corresponding authors had full access to all data and the final responsibility to submit the manuscript for publication. Results Patient Population Accrual was stopped before the inclusion of 50 patients because of the approval of sorafenib for the first-line systemic treatment of patients with advanced HCC. Of the 48 patients enrolled in May 2005 to December 2007, 43 received at least one dose of bevacizumab. Five patients did not receive treatment because of rapid liver failure (three patients), early disease progression (one patient), and stroke (one patient). Those five patients died between 23 and 74 days after registration and were excluded from all analyses. More than half of the patients.