Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.
Introduction: Ado-trastuzumab emtansine (T-DM1) is an antibody–drug conjugate and its survival advantage has been shown in advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer. However, clinical trials underrepresent patients ⩾65 years of age, leading to a lack of information in this population. We analyzed the real-world outcomes of older women who were treated with T-DM1 therapy. Methods: We performed a multicenter, observational, retrospective analysis of patients aged ⩾65 years treated with T-DM1. A total of 93 patients from 10 cancer centers were involved in the study. Our goal was to determine the survival, response rates, and toxicity profile in T-DM1–treated patients, as well as the factors that influence survival. Results: Median follow-up was 12.2 months. Objective response rate was 29%. Median progression-free survival (PFS) and overall survival (OS) were 8.47 and 15.0 months, respectively. In multivariate analysis, Eastern Cooperative Oncology Group Performance Score 2 was found to be an independent prognostic factor for worse PFS (hazard ratio [HR] 1.81, p = 0.032) and OS (HR 2.33, p = 0.006). Any adverse event (AE) was seen in 92.5% of patients; grade 3 or 4 AEs were seen in 30.1%. Dose reduction or treatment discontinuation rates were 11.8% and 6.5%, respectively. Conclusion: The efficacy of T-DM1 was acceptable and it was generally well-tolerated among older patients with advanced HER2-positive breast cancer.
A cetaminophen, which is understood to be the active metabolite of phenacetin and acetanilide, which Von Mering first used in 1893, was widely used after World War II. [1][2][3] The average dose for antipyretic and analgesic effects is 1 gram per day. It is administered at a dose of 0.5-1 g 3-4 times a day at most. Acetaminophen toxicity particularly leads to impairment of liver and kidney function. Toxicity occurs at a single dose of 10 grams or doses above 150 mg/ kg on average.Acetaminophen metabolism occurs mainly in the liver and to a lesser extent in the kidneys and intestines. There are three main mechanisms in liver metabolism: glucuronide conjugation, sulfate conjugation, and cytochrome p450 microsomal oxidation. [2][3][4][5][6] The primary metabolism takes place by glucuronide conjugation with uridine diphosphate glucuronodyl transferase. It is a toxic metabolite of N-acetyl-P-Benzoquinone Imine (NAPQI), which is formed due to the microsomal oxidation of the drug due to cyp450. This toxic Objectives: Acetaminophen can cause liver damage that can result with death when it is taken as high doses. In our study we proposed to examine the silymarin effect on acetaminophen induced hepatotoxicity. Methods: In this study, 40 wistar albino rats are randomly divided into 4 groups. 1 ml 0.9% serum physiologic was injected to intraperitoneal (IP) area in control group (group 1). 100 mg/kg silymarin was also injected to IP area in second group (group 2). 1250 mg/kg acetaminophen was injected to IP area in toxic group (group 3). And after 4 hours 1250 mg/kg IP injection of acetaminophen to treatment group (group 4) 100 mg/kg of silymarin was administered to this group. All rats were sacrificed after 24 hours. Results: In treatment group, acetaminophen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutamyltransferase, total bilirubin, direct bilirubin levels which are found increased in toxic group, are found as decreased and statistically significant. The malondialdehyde, a lipid peroksidation product, levels are high in toxic group and low in treatment group and it was statistically significant. There was no significant difference between groups, liver histopathological features. Conclusion: With this findings it can be assumed that silymarin has hepatoprotective effect.
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