We postulate that this modified administration of EC-BUD may be an effective therapeutic modality for olmesartan-induced enteropathy. It may likewise be an appropriate adjunct to other conditions involving widespread gastrointestinal inflammation, including eosinophilic gastroenteritis and gastrointestinal graft versus host disease.
Secondary failure of platelet recovery (SFPR) is a serious complication observed in approximately 20% of allogeneic hematopoietic stem cell transplant (HSCT) recipients. Although the standard therapeutic approach has been frequent platelet transfusions, romiplostim, a thrombopoietin receptor agonist, may have utility in treating SFPR. The primary objective of this single-center retrospective analysis was to assess effectiveness of romiplostim for SFPR and to evaluate patient factors which may influence clinical outcomes. The primary outcome measure of response was defined as achievement of platelet count ≥ 50 × 109/L without transfusions for ≥ 7 consecutive days. During the study period, 93 patients underwent HSCT and 13 (13.9%) received romiplostim for SFPR. Seven patients (53.8%) responded to romiplostim, requiring a median of three doses (range 1-6) to achieve independence from platelet transfusions. Disease relapse occurred in 38.5% of all patients, two responders and three nonresponders. Median survival post-HSCT was 753 days among responders and 266 days among nonresponders ( p = 0.0375). No serious adverse events were reported, and rates of graft-versus-host disease did not increase following administration of romiplostim. Thrombopoietin receptor agonists including romiplostim offer a treatment option for persistent thrombocytopenia following HSCT. Positive clinical response to romiplostim post-HSCT is associated with improved outcomes.
Paclitaxel is a potent chemotherapy for many cancers but it suffers from very poor solubility. Consequently the TAXOL formulation uses copious amounts of the surfactant Cremophor EL to solubilize the drug for injection resulting in severe hypersensitivity and neutropenia. In contrast to Cremophor EL, presented is a way to solubilize paclitaxel (PTX) by conjugation of a dicarboxylic fatty acid for specific binding to the ubiquitous protein, serum albumin. The conjugation chemistry was simplified to a single step using the activated anhydride form of 3-pentadecylglutaric (PDG) acid which is reactive to a variety of nucleophiles. The PDG derivative is less cytotoxic than the parent compound and was found to slowly hydrolyze to PTX (~5% over 72 h) in serum, tumor cytosol, and tumor tissue homogenate. When injected intravenously to tumor bearing mice, [3H]-PTX in the TAXOL formulation was cleared rapidly with a half-life of 7 hours. In the case of the PDG derivative of PTX, the drug is quickly distributed and approximately 20% of the injected dose remained in the vasculature experiencing a 23-h half-life. These improvements from modifying PTX with the PDG fatty acid present the opportunity for PDG to become a generic modification for the improvement of many therapeutics.
Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747-750) or exon 21 substitution mutation (L858R) is well-documented and supported.
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