2516 Background: Small molecule inhibitors of histone deacetylase (HDAC) have emerged as novel anticancer agents. MGCD0103 is an oral isotype selective small molecule inhibitor of HDAC. Methods: Eligible patients had relapsed/refractory (RR) AML or MDS (or newly diagnosed disease in patients >60 yrs, ineligible for induction chemotherapy); RR ALL; RR CML. MGCD0103 was administered 2x/weekly for 3 weeks, with no recovery period between cycles. Patients with stable disease or better were eligible to continue therapy indefinitely. Results: Patients have been treated at 4 dose levels: 40, 53, 66 and 83 mg/m2/day, including 19 enrolled patients with the following demographics: M:F = 15:4, median age (range) = 75 (52–83), ECOG 0:1:2 = 5:12:2, diagnosis of RR MDS= 7, RR AML or RR ALL=8: untreated AML or MDS = 4. Cytogenetics (n=12): Diploid = 3, Complex = 4, Del 7 = 3, Del 12 = 1, Del Y = 1. Nineteen patients are evaluable for safety. A total of 38 cycles have been administered with a median of 2 per patient (range, 1–6); 13 patients have completed =2 cycles. One patient experienced grade 3 fatigue at 53 mg/m2 and 2 patients had grade 3 weakness/fatigue at 83 mg/m2 (exceeded the Maximum Tolerated Dose [MTD]) Non-dose-limiting toxicities included lower grade fatigue, diarrhea, and nausea. Plasma PK in 14 patients revealed t 1/2 of 7–12 hr, tmax 0.6- 1 hr, and a dose proportional average Cmax of 155 ng/mL at 40 mg/m2 and 225 ng/mL at 53 mg/m2. Significant inhibition of whole cell total HDAC activity within PBMC was observed in a majority of patients, at all dosing levels. Four patients have experienced stable disease. Conclusions: MGCD0103 has been well-tolerated in patients with advanced leukemias or MDS. MTD has been reached, and the recommended phase II 2x/week dose is being confirmed. At all dose levels, significant HDAC inhibition was observed. [Table: see text]

Creation of a transabdominal transdiaphragmatic pericardial window for life-threatening recurrent pericardial effusion has proved to be a safe minimally invasive technique. By inducing adequate pericardial sac decompression while avoiding single-lung ventilation and thoracic drainage in severely ill patients, it provides anatomopathologic diagnosis and can direct further therapeutic measures. The transabdominal approach improves postoperative recovery dramatically by limiting postoperative pain and prevents sometimes invalidating intercostal neuralgia. Transabdominal pericardial sac fenestration should be part of the armamentarium used by every minimally invasive surgeon.