The MS-275 oral formulation on the daily schedule was intolerable at a dose and schedule explored. The q14-day schedule is reasonably well tolerated. Histone deacetylase inhibition was observed in peripheral-blood mononuclear-cells. Based on PK data from the q14-day schedule, a more frequent dosing schedule, weekly x 4, repeated every 6 weeks is presently being evaluated.

Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.

After completing this course, the reader should be able to:1. Describe the clinical trial that led to the approval of lapatinib in combination with capecitabine for the treatment of previously treated patients with HER-2-overexpressing metastatic breast cancer.2. Determine appropriate patients to receive lapatinib plus capecitabine treatment.3. Assess and manage the toxicities of lapatinib plus capecitabine treatment.This article is available for continuing medical education credit at CME.TheOncologist.com. ter TTP results of a prespecified interim analysis were made available, study enrollment was discontinued (399 patients enrolled). CME CME ABSTRACTThe median TTP was 27.1 versus 18.6 weeks (hazard ratio, 0.57; p ‫؍‬ .00013) favoring the lapatinib plus capecitabine arm. Response rates were 23.7% (lapatinib plus capecitabine) versus 13.9% (capecitabine alone). Survival data were not mature.Although the toxicities observed in the lapatinib and capecitabine combination arm were generally similar to those in the capecitabine alone arm, a higher incidence of diarrhea and rash was noted with the combination. Grade 3 or 4 adverse reactions that occurred with a frequency of >5% in patients on the combination arm were diarrhea (13%) and palmar-plantar erythrodysesthesia (12%). There was a 2% incidence of reversible decreased left ventricular function in the combination arm.

Purpose: MS-275 is a histone deacetylase inhibitor that has shown potent and unique anticancer activity in preclinical models.The aims of this phase I trial were to determine the dose-limiting toxicities and maximum tolerated dose of oral MS-275 in humans administered with food on a once weekly schedule and to study the pharmacokinetics of oral MS-275. Experimental Design: Patients with refractory solid tumors and lymphoid malignancies were treated with oral MS-275 on a once weekly schedule for 4 weeks of a 6-week cycle. Samples for pharmacokinetic and pharmacodynamic analyses were collected during cycle 1. Protein acetylation in subpopulations of peripheral blood mononuclear cells was measured using a multivariable flow cytometry assay. Results: A total of 22 patients were enrolled, and 19 were considered evaluable for toxicity. The maximum tolerated dose was 6 mg/m 2 . No National Cancer Institute CommonToxicity Criteria grade 4 toxicities were observed. Dose-limiting grade 3 toxicities were reversible and consisted of hypophosphatemia, hyponatremia, and hypoalbuminemia. Non^dose-limiting grade 3 myelosuppression was also observed. The mean terminal half-life of MS-275 was 33.9 F 26.2 and the T max ranged from 0.5 to 24 h. Although there was considerable interpatient variability in pharmacokinetics, the areaunder the plasma concentrationversus time curveincreasedlinearly withdose. Conclusions: MS-275 is well tolerated at a dose of 6 mg/m 2 administered weekly with food for 4 weeks every 6 weeks. Drug exposure increases linearly with dose, and protein acetylation increased in all the subpopulations of peripheral blood mononuclear cells following MS-275 administration.

IMPORTANCE In 2011, the US Centers for Medicare & Medicaid Services (CMS) changed its reimbursement policy for hemodialysis to a bundled comprehensive payment system that included the cost of erythrocyte-stimulating agents (ESAs). Also in 2011, the US Food and Drug Administration revised the drug label for ESAs, recommending more conservative dosing in patients with chronic kidney disease. In response to concerns that these measures could have adverse effects on patient care and outcomes, the CMS and the FDA initiated a collaboration to assess the effect. OBJECTIVE To assess the effects of the changes in reimbursement policy and the ESA drug label on patients who underwent incident hemodialysis. DESIGN, SETTING, AND PARTICIPANTS For this retrospective cohort study, patients 66 years or older who had undergone incident hemodialysis, and were enrolled in Medicare parts A, B, or D for at least 12 months prior to hemodialysis initiation between January 1, 2008, and December 31, 2013, were recruited from hemodialysis centers across the United States. Patients were divided into 2 cohorts based on their date of hemodialysis initiation and followed:

Perifosine given according to a loading and maintenance schedule can safely sustain concentrations of drug, approaching concentrations achieved in preclinical models with evidence of anti-tumor effect.

The current analysis has eliminated a number of candidate covariates from further consideration as important determinants of MS-275 absorption and disposition. Furthermore, MS-275 can be added to the list of cancer drugs where BSA-based dosing is not more accurate than fixed dosing.

Physiological fluorodeoxyglucose (FDG) uptake can obscure underlying disease or can even falsely suggest disease in patients undergoing whole-body positron emission tomography (PET) scanning for disease staging. Myocardial uptake in particular can present a problem because of its variability in fasting patients. Nonetheless, we present 2 cases in which FDG PET imaging was effective in identifying metastatic disease to the heart. In 1 case, an FDG PET scan revealed previously unsuspected myocardial metastases. In another case, FDG PET was useful in characterizing an intraatrial mass seen on anatomic imaging as a metabolically active lesion.