This ongoing, randomized phase III study assesses the safety and efficacy of entecavir versus placebo in nucleos(t)ide-na€ ıve children (2 to <18 years) with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B (CHB). Blinded treatment was administered for a minimum of 48 weeks. After week 48, patients with HBeAg seroconversion continued blinded treatment; those without switched to open-label entecavir. The primary endpoint was HBeAg seroconversion and HBV DNA <50 IU/mL at week 48. A total of 180 patients were randomized (2:1) and treated. Baseline median age was 12 years, with approximately 50% of children ages >12 to <18, and 25% each ages !2 to £ 6 and >6 to £ 12. Rates for the primary endpoint at week 48 were significantly higher with entecavir than placebo (24.2% [29 of 120] 60]; P 5 0.0210). Among entecavir-randomized patients, there was an increase in all efficacy endpoints between weeks 48 and 96, including an increase from 49% to 64% in virological suppression. The cumulative probability of emergent entecavir resistance through years 1 and 2 of entecavir was 0.6% and 2.6%, respectively. Entecavir was well tolerated with no observed differences in adverse events or changes in growth compared with placebo. Conclusion: In childhood CHB, entecavir demonstrated superior antiviral efficacy to placebo with a favorable safety profile. These results support the use of entecavir as a therapeutic option in children and adolescents with CHB.

A once-daily regimen of emtricitabine, didanosine, and efavirenz proved to be safe and tolerable and demonstrated good immunologic and virologic efficacy in this 2-year study.

Vincristine sulfate liposome injection (VSLI,) is a sphingomyelin and cholesterol nanoparticle formulation of vincristine sulfate (VCR) that was designed to overcome the dosing and pharmacokinetic limitations of standard VCR. In contrast to the rapid CL and wide tissue distribution of non-liposomal VCR, VSLI circulates in plasma for a prolonged period of time, with a slow CL of 345 mL/h and relatively small Vd of 3,570 mL. This facilitates enhanced and prolonged tumor-tissue delivery of VCR. The maximum tolerated dose of VSLI, 2.25 mg/m(2) once per week without a dose cap, enables individual and cumulative VCR exposure unachievable with non-liposomal VCR at its labeled dose of 1.4 mg/m(2) . VSLI is associated with a dose-dependent peripheral neurotoxicity albeit at doses that are two to three times that of standard VCR. VCR dose intensification with VSLI correlated with an increased probability of overall response and a strong trend towards increased complete response in adults with relapsed and/or refractory acute lymphoblastic leukemia. Overall, VSLI improves the therapeutic index by facilitating increased dose intensification while maintaining a predictable and manageable safety profile.

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.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 g/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 g/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.