miR-148b regulates radioresistance of lung cancer cells by modulating MLH1 expression level.
Background Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. Methods Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan–Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. Results Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6–5.4%), and DCR was 35.8% (95% CI, 33.7–38.0%). The median PFS was 2.7 months (95% CI 2.2–2.8), and the median OS was 5.8 months (95% CI 5.4–6.1). Conclusions The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. Trial registration This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.
35 Background: A fine balance between maintaining efficacy and reducing toxicity is necessary for drug therapies in many cancers. This study seeks to review the data from phase IV clinical trial of Ahead-G201 to help elucidate the optimal initial dose of apatinib in advanced gastric cancer. Methods: Pts data from the Ahead-G201 study at cut-off date of Jul 10, 2017 were extracted to explore the correlation of apatinib initial dose (500 mg vs 850 mg) with safety and clinical efficacy. Results: 864 of eligible pts received apatinib at an initial dose of 500 mg, and 58 pts received at 850 mg. Dose interruption occurred in 258 pts (33.1%) at 500 mg and in 27 pts (46.5%) at 850 mg. For safety, the most common adverse events (AEs) were proteinuria, hypertension and leukocyte decrease in both groups. Moreover, the incidence of all AEs and grade 3-4 AEs in pts at 500 mg was significantly lower than pts at 850 mg (Table). For efficacy, pts at 500 mg achieved an objective response rate (ORR) of 10.8% and a disease control rate (DCR) of 70.6%, at best response, which were 10.3% and 55.2% in pts at 850 mg. Pts at 500 mg got a significantly longer median progression-free survival (mPFS) and median overall survival (mOS) than pts at 850 mg (PFS, 4.6 mos vs 2.2 mos; OS, 6.8 mos vs 4.0 mos). Multivariate analysis indicated that apatinib treatment at an initial dose of 500 mg was significantly associated with longer mOS in advanced gastric cancer pts (6.8 mos vs 4.0 mos: hazard ratio, 0.5; 95%CI, 0.3 to 0.8), compared to initial dose of 850 mg. Conclusions: Compared to receiving apatinib at initial dose of 850mg, oral administration of apatinib starting from 500 mg seemed to bring more clinical benefit for patients with advanced gastric cancer, whilst with lower toxicities. Clinical trial information: NCT02426034. [Table: see text]
In the present study, the IER3 expression was examined in tumor tissue from PHC patients to determine whether the IER3 expression is correlated with other clinicopathological parameters. Materials and Methods Sample selectionSixty-two pathologically conformed human HCC specimens without preoprative therapy, such as chemotherapy and radiotherapy, were collected at the pathology department of Zibo center hospital. All specimens were fixed in bufered 4% para formaldehyde, embedded in paraffin. The procedures were performed according to the national institutes of health guidelines regarding the use of human tissues and the study was approved from the review board of the ethics committee of Zibo center hospital. RNA isolation and cDNA conversionRNA was extracted from FFPE tissues using the Relia prep TM FFPE total RNA Miniprep system and based on the manufacturer's recommendation (Promega, 1002). Briefly, six shaving 10 μm thick from a paraffin block of tissue were deparaffinized by washing the tissue with xylene. Tissue was then digested in protease K and allowed to adhere to the RNA biding column.
142 Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. Due to toxicity, many pts underwent temporary interruptions during treatment. We analyzed the data from a phase IV clinical trial of Ahead-G201 to evaluate the relationship between dose interruption, drug safety and efficacy. Methods: At the cutoff date of Jul 10, 2017, Ahead-G201 study enrolled 1037 pts. The adverse events (AEs) and clinical efficacy were evaluated for pts with no, 1, 2 and ≥3 dose interruptions. Results: 336 of 1037 pts underwent dose interruptions during apatinib treatment: 1 interruption in 183 pts; 2 interruptions in 67 pts; and ≥3 interruptions in 86 pts. The toxicity and efficacy for them were listed in Table. For safety, pts with no interruption had the lowest incidence of all AEs (59.3%) and grade 3-4 AEs (30.0%). Pts with ≥3 interruptions had the highest objective response rate (ORR, 20.3%) and disease control rate (DCR, 82.6%). Moreover, these pts got median progression-free survival (mPFS) of 6.6 mos and median overall survival (mOS) of 9.4 mos, which were the longest among 4 groups. Furthermore, multivariate analysis revealed that ≥3 interruptions of apatinib bring much more efficacy benefit both in mPFS (6.6 vs 3.8 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.7) and mOS (9.4 vs 6.6 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.8) for pts, than those with no interruption. Conclusions: Current results indicated that dose interruptions are required to manage toxicity and it is necessary to explore an optimal dosing pattern of apatinib in advanced gastric cancer. Clinical trial information: NCT02426034. [Table: see text]
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.