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As the use of immune checkpoint inhibitors for several different malignancies becomes more mainstream, their side-effect profile raises new challenges. In 2011, the Food and Drug Administration approved the first checkpoint inhibitor for the treatment of advanced melanoma, and since then, checkpoint inhibitors have demonstrated efficacy in many other tumor types. Given the frequent use of immune checkpoint inhibitors in a wide range of cancers today, the diagnosis and management of their immune-mediated toxicities need special attention. One of the most common is immune-mediated colitis. Workup and management of immune-mediated colitis can be challenging and is the purpose of this review. KEY POINTS Rate of immune mediated colitis differ from different kind of immune checkpoint inhibitor treatment. To work up immune-mediated colitis, tests to rule out infectious etiologies of diarrhea, colonoscopy and abdominal image will help to differentiate immune mediated colitis from colitis from other etiology. Patients with mild colitis can be managed with supportive therapies alone, but more severe cases may require immunomodulators such as steroid. Refractory cases may require tumor necrosis factor (TNF) inhibitors, such as infliximab in addition to steroid treatment. © AlphaMed Press 2019.BACKGROUND The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p less then .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity. © AlphaMed Press 2019.BACKGROUND In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail. MATERIALS AND METHODS Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time-varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient-reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms. RESULTS The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3-4 months of receiving talazoparib. ib was generally well tolerated in patients with germline BRCA-mutated HER2-negative advanced breast cancer in the EMBRACA trial. Common toxicities with talazoparib were primarily hematologic and infrequently resulted in permanent drug discontinuation ( less then 2% of patients discontinued talazoparib due to hematologic toxicity). Hematologic toxicities typically occurred during the first 3-4 months of treatment and were managed by dose modifications and supportive care measures. A significant efficacy benefit, improved patient-reported outcomes, lower rate of health resource utilization and a tolerable safety profile support incorporating talazoparib into routine management of germline BRCA-mutated locally advanced/metastatic breast cancer. © 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.LESSONS LEARNED It is possible to plan and treat some patients with stereotactic body radiotherapy (SBRT) in a timely fashion in an acute setting. Advanced and, in some indications, already implemented technologies such as SBRT are difficult to test in a randomized trial. BACKGROUND Stereotactic body radiotherapy (SBRT) in metastatic spinal cord compression (MSCC) could be an alternative to decompressive surgery followed by fractionated radiotherapy. METHODS In a randomized, single-institution, noninferiority trial, patients with MSCC were assigned to stereotactic body radiotherapy of 16 Gy in 1 fraction or decompression surgery followed by fractionated radiotherapy of 30 Gy in 10 fractions. Propionyl-L-carnitine cost Primary endpoint was ability to walk by EQ5D-5L questionnaire. Based on power calculations, 130 patients had to be included to be 89% sure that a 15% difference between the treatment arm and the experimental arm could be detected. RESULTS Ten patients were accrued in 23 months, with six patients allocated to surgery and four patients to stereotactic body radiotherapy. The trial was closed prematurely because of poor accrual. One patient undergoing surgery and one patient undergoing stereotactic body radiotherapy were unable to walk at 6 weeks. Two patients were not evaluable at 6 weeks. CONCLUSION A randomized, phase II, clinical trial comparing surgery followed by fractionated radiotherapy or image-guided SBRT of MSCC was initiated. SBRT was shown to be feasible, with three out of four patients retaining walking function. The trial was determined futile as a result of low accrual. © AlphaMed Press; the data published online to support this summary are the property of the authors.Anti-programmed cell death protein-1 (anti-PD-1) therapy has greatly improved outcomes of patients with melanoma; however, many fail to respond. Although preclinical studies suggest a potentially synergistic relationship with anti-PD-1 therapy and certain concurrent medications, their clinical role remains unclear. Here, we retrospectively evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and other drugs in 330 patients with melanoma treated with anti-PD-1 therapy from four academic centers. In the cohort, 37% of patients used NSAIDs including aspirin (acetylsalicylic acid; ASA; 47%), cyclooxygenase (COX)-2 inhibitors (2%), and non-ASA/nonselective COX inhibitor NSAIDs (59%). The objective response rates (ORRs) were similar in patients with NSAID (43.4%) and no NSAID (41.3%) use with no significant difference in overall suvival (OS). There was a trend toward improved progression-free survival (PFS) in patients who took NSAIDs (median PFS 8.5 vs. 5.2 months; p = .054). Most patients (71.3%) took NSAIDs once daily or as needed.
Read More: https://www.selleckchem.com/products/propionyl-l-carnitine-hydrochloride.html
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