Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown great results in numerous clinical trials and have improved the clinical outcome for patients with hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer significantly. To date, three CDK4/6 inhibitors are approved by the US Food and Drug Administration (FDA): palbociclib, ribociclib and abemaciclib; the first two compounds are aproved by the European Medicines Agency (EMA) as well. In combination with endocrine therapy, all of them led to significantly improved progression-free survival compared with endocrine therapy alone. The aim of this article is to give an overview of the efficacy data and to describe the CDK4/6 inhibitor-based treatment-associated adverse events, including hematological and nonhematological adverse events. In addition, it describes the corrrect approach to patient monitoring and adverse event mangement and summarizes the current recommendations for dose reductions and dose interruptions regarding the key adverse events, such as neutropenia, diarrhea, QTc prolongation and hepatobiliary toxicity. Accurate patient monitoring and management of the side effects is crucial, as several clinical trials in early breast cancer are in progress and may lead to an additional approval in the neo-/adjuvant setting.
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PMID:Management of adverse events during cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based treatment in breast cancer. 3057 8

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are now the standard of care for hormone receptor-positive (HR+), HER2-negative (HER-) metastatic breast cancer (MBC). However, guidelines are lacking regarding their optimal sequencing with other available agents. This study examines physician practice patterns and treatment outcomes of palbociclib and subsequent therapies in a real-world setting. Methods: A retrospective chart review was conducted for consecutive patients with MBC who received palbociclib between February 2015 and August 2017 at the Alvin J. Siteman Cancer Center. Kaplan-Meier method was used to generate time-to-event curves and estimate median progression-free survival (mPFS). Log-rank test was used to compare differences. Results: A total of 200 patients, with a median age of 59.4 years and a follow-up of 19.5 months, were included. Palbociclib was most frequently combined with letrozole (73.5%), followed by fulvestrant (25%), anastrozole (1%), and tamoxifen (0.5%). Most patients received palbociclib in the endocrine-resistant setting (n=42, n=50, and n=108 in the first-, second-, and subsequent-line settings, respectively), and the fraction of patients receiving palbociclib as first- or second-line therapy increased in recent months (P=.0428). mPFS was 20.7, 12.8, and 4.0 months with palbociclib administered in the first-, second-, and subsequent-line settings, respectively (P<.0001). Incidences of grade 3/4 neutropenia (41.5%) and dose reductions (29%) were comparable to reports in the literature. Among patients whose disease progressed on palbociclib (n=104), the most frequent next-line treatment was capecitabine (n=21), followed by eribulin (n=16), nab-paclitaxel (n=15), and exemestane + everolimus (n=12). mPFS with hormone therapy alone or in combination with targeted agents (n=32) after first-, second-, and subsequent-line palbociclib was 17.0, 9.3, and 4.2 months, respectively (P=.04). mPFS with chemotherapy (n=70) was not reached, 4.7, and 4.1 months after first-, second-, and subsequent-line palbociclib, respectively (P=.56). Conclusions: Palbociclib is effective for HR+/HER2- MBC in real-world practice. Hormone therapy alone or in combination with targeted agents remains an effective option after palbociclib progression.
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PMID:Retrospective Analysis of Treatment Patterns and Effectiveness of Palbociclib and Subsequent Regimens in Metastatic Breast Cancer. 3078 27

Cyclin-dependent kinase (CDK) 4/6 inhibitors have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. They have been shown to double the efficacy of endocrine-based treatment. Three oral agents are available to date: palbociclib, ribociclib, and abemaciclib. The aim of this article is to give a short overview of the existing efficacy data, to summarize the recommended clinical monitoring procedures for patients under CDK4/6 inhibitors, and to shed light on the clinical management of the most common treatment-emergent adverse events. The hematological class side effect neutropenia as well as non-hematological toxicities (e.g., impaired liver function, prolonged QTc interval, and diarrhea) are discussed. In addition, the current knowledge about relevant drug interactions is reviewed.
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PMID:Management of Adverse Events Due to Cyclin-Dependent Kinase 4/6 Inhibitors. 3223 5