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Aim: The phase III REFLECT study utilized bodyweight‐based lenvatinib dosing in patients with unresectable hepatocellular carcinoma, based on results of the phase II Study 202. This post hoc analysis compared efficacy and safety in patients with lower and higher bodyweights. Methods: This comparison included patients from Study 202 (Japanese, n = 43; Korean, n = 3) and Japanese patients from REFLECT (n = 81) who received lenvatinib. In Study 202, all patients received a starting dose of lenvatinib 12 mg/day; in REFLECT, patients received starting doses based on bodyweight (patients <60 kg, 8 mg/day; ≥60 kg, 12 mg/day). Safety and efficacy were assessed in both studies according to bodyweight. Results: In Study 202, treatment‐related, treatment‐emergent adverse events (TEAEs) led to dose reductions in 80.8% and 55.0% of patients in the lower and higher bodyweight groups, respectively. In REFLECT, treatment‐related TEAEs led to dose reductions in 52.5% and 70.7% of patients in the 8 and 12 mg groups, respectively. In Study 202, median overall survival (OS) was 16.2 months (95% confidence interval [CI], 9.8–25.1) and 21.3 months (95% CI, 10.1–not estimable) in the lower and higher bodyweight groups, respectively. In REFLECT, median OS was 15.8 months (95% CI, 10.4–27.6) and 18.2 months (95% CI, 11.3–26.9) in the 8 and 12 mg groups, respectively. Conclusions: Comparison between patients in Study 202 and REFLECT demonstrates efficacy was maintained with improved safety in patients with lower bodyweights who received lenvatinib 8 mg/day in REFLECT versus patients who received lenvatinib 12 mg/day in Study 202. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) accounts for up to 90% of primary liver cancer occurrences worldwide. Lenvatinib, a multikinase inhibitor, was approved in radioiodine-refractory differentiated thyroid cancer. In this phase 2 study (study 202), we aimed to identify the lenvatinib optimal dose for subjects with advanced HCC Child-Pugh class A. Pooled data from phase 1 studies in healthy adults and in subjects with mixed tumor types, and from study 202 in subjects with HCC, were analyzed using a population pharmacokinetic approach. The relationship between treatment-emergent adverse events leading to withdrawal or dose reduction during cycle 1 and lenvatinib exposure was explored by logistic regression analysis. A receiver operating characteristics analysis was used to investigate the best cutoff values of lenvatinib exposure and body weight to identify a high-risk group for early dose modification. The final pharmacokinetic model included body-weight effects on apparent clearance and volume. The relationship between the lenvatinib area under the plasma concentration-time curve (AUC) at steady state and body weight demonstrated an increase in AUC as body weight decreased in subjects with HCC. An exposure-response relationship was observed, with higher lenvatinib AUC and lower body weight resulting in earlier drug withdrawal or dose reduction. The best cutoff values for body weight and lenvatinib AUC were 57.8 kg and 2430 ng·h/mL, respectively, to predict the group at high risk for early drug withdrawal or dose reduction. We therefore recommend 12-mg and 8-mg starting doses for subjects ≥60 kg and <60 kg, respectively, in subjects with HCC Child-Pugh class A. [ABSTRACT FROM AUTHOR]

ABSTRACT We present in-situ formation of metal nanoparticle/acrylic polymer hybrid and its application to prepare hybrid latex particles by miniemulsion polymerization. On the surface of a silver nanoparticle/silica nanoparticle/acrylic polymer hybrid layer formed in-situ on a polyethylene terephthalate (PET) substrate, a copper film is deposited using electroless copper deposition. Silver nanoparticles, which are formed in-situ via the reduction of silver ion by radical species and subsequent annealing, work as a catalyst for the electroless deposition. Miniemulsion polymerization via the in-situ formation of nanoparticles affords nanoparticle/acrylic polymer hybrid latex particles and polymer particles. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42675. [ABSTRACT FROM AUTHOR]