Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy.

PURPOSE: To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy. PATIENTS AND METHODS: This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly. RESULTS: The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, -3.8 to +5.3) compared with 2.8 g/dL (range, -2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256 units of RBCs compared with 127 units in the epoetin group (P < .0001). The incidence of toxicity in the groups was similar. Changes in the average QOL scores from baseline to the end of the study were similar in the two groups (P = not significant). The HgB responders (irrespective of treatment arm) had a mean change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a baseline of +5.1 compared with -2.1 for the nonresponders (P = .006). CONCLUSION: Epoetin alfa significantly improved HgB and reduced transfusions in this patient population. These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia.     

Influence of intensive lipid‐lowering on CT derived fractional flow reserve in patients with stable chest pain: Rationale and design of the FLOWPROMOTE study

IntroductionCoronary CT angiography (CTA) derived fractional flow reserve (FFR_CT) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated.AimTo test whether lipid lowering therapy is associated with significant improvement in FFR_CT, and whether there is a dose–response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery.MethodsInvestigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first‐line CTA, and FFR_CT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFR_CT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18‐month difference in FFR_CT using (1) the FFR_CT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study.ConclusionThe results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.     

Inhaled drug therapy development for the treatment of migraine

Introduction: The inhalation of substances, both medicinally and recreationally, is a commonly used method of drug administration but has been underutilized in the treatment of neurologic disorders such as migraine. Three drugs have been studied as potential inhalable treatments for acute migraine: dihydroergotamine (MAP0004), prochlorperazine (Staccato prochlorperazine), and loxapine (Staccato loxapine).

Areas covered: This review discusses the available literature describing the pharmacokinetics, tolerability and efficacy of MAP0004, Staccato prochlorperazine and Staccato loxapine, including data from Phase II and Phase III clinical trials.

Expert opinion: Inhaled DHE offers rapid absorption with a pharmacokinetic profile similar to IV administration. Improved side effect profile results from more selective binding at antimigraine serotonergic receptors 5-HT_1B and 5-HT_1D. Inhaled prochlorperazine is rapidly absorbed and resulted in statistically significant migraine pain relief at 2 hours compared to placebo but is not currently being pursued by the manufacturer as a potential migraine abortive. Inhaled loxapine is also rapidly absorbed into systemic circulation but Phase IIb trials did not show statistically improved pain relief or pain freedom compared to placebo. MAP0004 will likely provide a good alternative to patients seeking rapid relief without the need for injection or other invasive routes.     

Intrathecal Central Nervous System Prophylaxis in Patients With Diffuse Large B-cell Lymphoma at an Academic Healthcare System

Introduction

Intrathecal chemoprophylaxis is often administered to patients with diffuse large B-cell lymphoma (DLBCL) to lower the rates of central nervous system (CNS) relapse, although its benefit has not been well-described. Prognostic models, including the CNS-International Prognostic Index (IPI), have been developed to aid in identifying patients at highest risk for CNS relapse.