epithelial malignancies.Eligibility criteria included histologically confirmed advanced thymoma or thymic carcinoma not amenable to potentially curative therapies, disease progression after failure of at least one prior line of platinum based chemotherapy, age older than 18 years, life expectancy more than 3 months, measurable disease according travoprost to RECIST criteria,9 Eastern Cooperative Oncology Group performance status of 2 or greater, and adequate organ and bone marrow function. Repeated demonstration of a correctedQT interval of more than 500msand long QT syndrome were exclusion criteria. No major surgery, radiotherapy, or systemic therapy was permitted up to 28 days before enrollment, and any residual toxicity had to have been resolved.
Patients with stable and treated brain metastases Itraconazole molecular weight and patients receiving steroids for myasthenia gravis or other autoimmune disorders were permitted to enroll. All patients provided written informed consent. Belinostat was diluted in 250 mL normal saline and infused intravenously over 30 minutes through a central venous catheter on days 1 to 5, every 21 days. After 12 cycles of treatment, patients were offered treatment every 4 weeks. Treatment was continued until disease progression or development of intolerable toxicity. Dose modifications were performed if patients developed severe toxicities. Assessment of disease extent at baseline was requested using computed tomography scans of the chest, abdomen, and pelvis; fluorodeoxyglucose positron emission tomography scans and additional imaging were recommended as required for proper assessment.
Electrocardiograms, blood cell Nelarabine price counts, and chemistries were also performed before registration. Blood cell counts were initially repeated weekly, but because no hematologic toxicity was observed, the protocol was amended to allow performance of blood cell counts before every cycle after 19 patients had been recruited. An electrocardiogram was performed every cycle at the end of belinostat infusion on day 5, and the need for dose modification for the subsequent cycles was determined. Asymptomatic increase of QTc more than 500 ms required 25% dose reduction once QTc returned to less than 500 ms. Dose reductions were allowed twice. Assessment of response was performed every two cycles according to RECIST criteria.9 After 12 cycles, computed tomography scans were repeated every three cycles.
Histology was determined according to WHO classification,10 and central review was required. Assessment of adverse effects was performed according to Common Terminology Criteria of Adverse Events . Pharmacodynamic Irinotecan ic50 Analyses: Protein Acetylation and Peripheral Blood Mononuclear Cell Immune Subsets Whole blood samples were collected in CPT tubes with sodium citrate on day 1 of cycle one, 1 hour after belinostat dosing on day 3 of cycle one, and before belinostat dosingonday 1 of cycle two. Mononuclear cells were obtained by Ficoll density gradient centrifugation , and the cells were viably frozen until analysis. Analysis of global protein and tubulin acetylation was performed by multi paramete rflowcytome try on an LSRII flowcyto meter, and data were analyzed using FlowJo software , as described byChunget al.11 Peripheral blood mononuclear protein kinases cellswere analyzed for immune subsets.