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“Ixabepilone
40 mg/m(2) administered on an every 3-week schedule is approved for use in metastatic breast cancer (MBC) as monotherapy, or in combination with capecitabine in anthracycline/taxane resistant tumors. Because the mechanism of action and toxicity profile is similar to the taxanes, it has been suggested that weekly administration (15-20 mg/m(2) on days 1, 8, 15 for 28 days/cycle) may provide a therapeutic advantage while minimizing toxicity. We report 24 MBC patients treated with weekly ixabepilone. Demographics, ER/PR/HER-2/neu, ECOG performance status (PS), sites of metastatic disease, lines of previous therapy, dosage, treatment duration, dose reductions/interruptions, hematologic/non-hematologic selleck kinase inhibitor toxicities, growth factor use, reasons for discontinuation, time to progression (TTP), and response rate were recorded. Median age was 61 years (33-79). 0-1 ECOG PS
was 54%. Sixty-seven percent of patients received >= 4 previous chemotherapy regimens. Median treatment duration was 1.4 months (0.5-10.8). Median dose was 16 mg/m(2) (15-20). In 37.5% of patients, the dose was held due to toxicities with median missed dose of 2. Partial response and stable disease were 4 and 48%. Median TTP was 2.1 months (0.9-16.4). Majority of patients discontinued therapy due to disease progression (84%). Grade 3-4 neutropenia and neuropathy were 4% and 8%. It is not yet clear whether
the weekly administration of ixabepilone impacts the risk/benefit profile. There are clinical data to suggest that weekly Alisertib mouse ixabepilone is efficacious and tolerable. Upcoming clinical trials will continue to inform the question. Our data suggest that weekly ixabepilone is well tolerated with a manageable side-effect profile in this small, heavily pretreated population.”
“Graft-versus-host disease (GVHD) is a donor T cell driven response against host tissue that can complicate allogeneic hematopoietic stem cell transplantation (HSCT). During acute GVHD, endogenous adjuvants such as uric acid are released by damaged host tissue, activating alloreactive donor T cells. A phase I study was conducted at the Massachusetts General Hospital between 2007 and 2010 to test the hypothesis A-1331852 mouse that reduction of uric acid levels during allogeneic HSCT can modulate the development of acute GVHD. Twenty-one patients with hematologic malignancies in complete remission undergoing myeloablative peripheral blood HSCT received recombinant urate oxidase at .20 mg/kg for 5 consecutive days during conditioning. Results were compared with all patients who underwent allogeneic HSCT at our institution during the same time period who met the same inclusion and exclusion criteria but were not enrolled in the study. The only major adverse event was a case of hemolytic anemia in a patient who had glucose-6-phosphate dehydrogenase deficiency.