A phase I study of panobinostat and ruxolitinib in patients with primary myelofibrosis (PMF) and post--polycythemia vera/essential thrombocythemia myelofibrosis (post--PV/ET MF).

Ruxolitinib, a selective JAK1/JAK2 inhibitor, is the current first line therapy for myelofibrosis (MF), which reduces symptomatology and splenomegaly, but does not clearly modify disease course. Panobinostat, a histone deacetylase inhibitor, was shown to be safe and tolerable in phase I and II trials and demonstrated clinical activity in approximately a third of treated patients. Combination therapy of ruxolitinib and panobinostat showed synergistic activity in a preclinical MF model, which prompted clinical evaluation of this combination in both ruxolitinib naïve and treated MF patients. Herein, we report the results of an investigator-initiated, dose escalation, phase I trial of ruxolitinib and panobinostat in 15 patients with primary MF and post-polycythemia vera/essential thrombocythemia MF. This combination treatment proved to be safe and tolerable without dose limiting thrombocytopenia and a maximum tolerated dose of both agents in combination was not determined. The majority of patients maintained stable disease with this combination treatment and 40 % attained a clinical improvement (spleen n = 5, anemia n = 1) by modified IWG-MRT at the end of 6 cycles. This is one of the first attempts of rationally designed, JAK inhibitor-based, combination therapy studies and exemplifies the feasibility of such an approach in patients with advanced MF.

Retrospective comparison of Adderall and methylphenidate in the treatment of attention deficit hyperactivity disorder.

Methylphenidate is the most frequently prescribed stimulant medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the short duration of action of methylphenidate requires that patients take multiple daily doses for optimal efficacy. Recent studies suggest that Adderall, a psychostimulant indicated for the treatment of ADHD, may provide an efficacious, less frequently dosed alternative to methylphenidate. This retrospective review compares the efficacy, safety, dosing frequency, and medication switch rates of Adderall with methylphenidate in children and adolescents with ADHD treated in a private, outpatient psychiatric clinic. Of the evaluable patients, 54 received Adderall, and 75 received methylphenidate. No statistically significant differences were noted between Adderall and methylphenidate in efficacy or safety parameters. Fewer patients receiving Adderall required twice daily, thrice daily, or in-school dosing than those receiving methylphenidate (p < 0.001). During the initial 6-month treatment period, patients treated with Adderall were less likely to switch medications than those receiving methylphenidate (p = 0.0002). In this analysis, Adderall and methylphenidate provided comparable efficacy and safety in children and adolescents with ADHD. The use of Adderall allowed patients to extend their dosing interval and reduced the need for in-school dosing, a measure that may substantially influence compliance.