Evaluation of the Efficacy of Sorafenib on Overall Survival in Patients with Hepatocellular Carcinoma using FT Rate: A Devised Index.

INTRODUCTION: Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate stage hepatocellular carcinoma (HCC) and prolongs survival in HCC patients. However, repeated TACE results in diminished therapeutic response. In addition, the superiority of sorafenib to TACE monotherapy or combined therapy in patients with HCC is still controversial. The prognosis of HCC has many variables and, thus, the effect of a specific treatment is difficult to evaluate. The frequency of treatments per year (FT rate) used in this study was obtained by dividing the total number of radiofrequency ablations and TACE or transcatheter arterial infusion treatments by the years of survival. The aim of this study was to evaluate the overall survival (OS) of TACE versus sorafenib using the FT rate. METHODS: We compared the OS of patients with recurrence of HCC receiving repeated TACE monotherapy (CON) with those receiving therapy switched from TACE to sorafenib (SOR). In addition, a one-to-one FT rate matching cohort consisting of matched SOR (mSOR) and matched CON (mCON) was determined using the propensity score matching method, and OS in the cohort was evaluated. Factors influencing survival were evaluated using Cox proportional hazard regression analysis in all patients and the FT rate matched cohort. RESULTS: In the FT rate matched cohort, the cumulative survival rate was significantly higher in the mSOR group compared with the mCON group. Multivariate regression analysis of the FT rate matched cohort showed the FT rate and sorafenib to be significant variables for survival with a hazard ratio (HR) of 2.86 (p < 0.001) and 0.42 (p = 0.008), respectively. CONCLUSION: Early switching from TACE to sorafenib therapy may prolong OS in HCC patients unresponsive to TACE. The present study indicates that the FT rate is potentially a useful index in evaluating the outcome for patients at various stages and treatment regimens. FUNDING: Bayer Yakuhin, Ltd.

Efficacy of transcatheter arterial chemoembolization followed by sorafenib for intermediate/advanced hepatocellular carcinoma in patients in Japan: a retrospective analysis.

BACKGROUND: Sorafenib might prevent hepatocellular carcinoma (HCC) recurrence caused by the promotion of neoangiogenesis after transarterial chemoembolization (TACE). OBJECTIVES: To evaluate the efficacy and safety of TACE followed by sorafenib for treating advanced HCC. PATIENTS AND METHODS: We retrospectively analyzed 95 advanced HCC patients treated with TACE between July 2008 and December 2012 at our institution. Twenty-four patients received TACE followed by sorafenib within 14 days (S-TACE) and 71 received TACE alone. Progression-free survival (PFS) and cumulative survival from the time of non-responsiveness to TACE were compared between groups and predictive factors for PFS were analyzed. RESULTS: The median patient age was 72.2 years and 74 patients were male (77.9 %). Although median tumor size was similar between groups, the mean tumor number was significantly higher in the S-TACE versus TACE-alone group (16 vs. 8, P = 0.04). The number of prior treatments was significantly higher in the S-TACE group. Other baseline variables were similar. There were two severe adverse events in the S-TACE group and none in the TACE-alone group. Median PFS (189 vs. 106 days, P = 0.02) and median overall survival time (861 vs. 467 days, P = 0.01) from the time of non-responsiveness to TACE were significantly longer with S-TACE than TACE alone. Adjusting for significant factors in univariate analysis, multivariate analysis indicated that sorafenib administration, tumor size, and alanine transaminase were independent predictors of PFS. CONCLUSION: TACE followed by sorafenib significantly improved PFS and survival in patients with advanced HCC unresponsive to TACE.

Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval.

The efficacy of antimicrobial regimens for the treatment of uncomplicated gonococcal urethritis depends partially upon the period of time (therapeutic time) during which the drug concentration in the blood after the concentration peak is greater than four times the minimum inhibitory concentration for 90% of clinical isolates of Neisseria gonorrhoeae (MIC(90)). A therapeutic time of at least 10 h is suggested as an important determinant for elimination of 95% or more of the infection. In this study, therapeutic times for a single 400-mg dose of cefixime at various MIC(90)s were calculated, and pharmacokinetic profiles of double-dosing of 200 mg cefixime at various intervals were simulated. Subsequently, a dosing interval of 6 h was tested in 6 healthy Japanese men, and then 93 Japanese men with gonococcal urethritis were treated with a regimen of two 200-mg doses of cefixime given at a 6-h interval. For a single dose of 400 mg cefixime, therapeutic times were calculated to be 12.8, 9.1, 5.4, and 1.7 h for MIC(90)s of 0.06, 0.125, 0.25, and 0.5 microg/ml, respectively. In the simulation study of double-dosing of 200 mg cefixime at a 6-h interval, the therapeutic times for the MIC(90)s of < or =0.125 microg/ml were longer than 10 h. Of the 93 patients, 68 were evaluated for microbiological outcome, and N. gonorrhoeae was eradicated in 60 (88.2%). The MIC(90) of cefixime for the 61 isolates tested was 0.125 microg/ml. All strains with MICs of < or =0.06 microg/ml were eradicated, whereas 8 of 16 strains with MICs of > or =0.125 microg/ml persisted after treatment. This regimen would not be effective against infection by strains exhibiting cefixime MIC(90)s of > or =0.125 microg/ml. For such strains, a different regimen with a higher dose of cefixime would be required.