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INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.
ABSTRACT
Background: Gallbladder papillary adenocarcinoma (GBPA) is an uncharacteristically gallbladder cancer subtype. Although some studies have shown that the prognosis of GBPA patients is significantly better than that of gallbladder adenocarcinoma (GBA) and gallbladder mucinous adenocarcinoma (GBMA) due to its rarity, there is a lack of large sample studies necessary to confirm the clinical characteristics and survival rate of GBPA. Therefore, this study aimed to describe the clinicopathological characteristics affecting survival in GBPA. This data was then used to establish a prognostic nomogram for GBPA. Methods: The data of patients diagnosed with gallbladder cancer between 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The clinical features and survival of patients with GBPA were compared with those of GBA and GBMA after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for GBPA. Subsequently, the overall survival (OS) and cancer-specific survival (CSS) nomograms were established to predict GBPA prognosis. The performance and discrimination of the nomogram were measured using concordance index (C-index), calibration curves, receptor operating characteristic curves(ROC), and decision curve analysis (DCA) was applied to examine the net benefit of tients with GBPA, 5798 patients with GBA, and 223 patients with GBMA. The mean 1-, 3- and 5-year OS rates for GBPA were 81.3%, 58.8%, and 49.1%, respectively, while the mean 1-, 3- and 5-year CSS rates were 85.0%, 68.1%, and 61.0%, respectively. The median OS rates was 58 months (95% CI: 43-88), while the median CSS was not reached. The PSM analysis showed a differ statistically significantly in the OS between GBPA and GBA. However, there has no statistically difference in CSS. Conversely, the OS and CSS between GBPA and GBMA have statistically significant differences. Age, marital, T stage, and M stage were strongly linked to the prognosis for OS, while T-stage, M-stage, and surgery were significantly associated with the prognosis for CSS in GBPA patients. The AUC for the 1-, 3-, and 5-year OS were 0.722 (95%CI: 0.630-0.813), 0.728 (95%CI: 0.665-0.790), and 0.706 (95%CI: 0.641-0.771), respectively. The AUC for the 1-, 3-, and 5-year CSS were 0.749 (95%CI: 0.659-0.840), 0.698 (95%CI: 0.627-0.770), and 0.665 (95%CI: 0.594-0.735), respectively. The C-indices for the OS and CSS nomograms were 0.701 (95% CI: 0.634-0.744) and 0.651 (95% CI: 0.598-0.703), respectively. The calibration curves showed that the nomograms were well consistency. The DCA showed that compared with the TNM system, the nomogram models had a significant positive net benefit in survival prediction. Conclusion: GBPA has distinct clinicopathological characteristics and survival compared to other gallbladder carcinomas. The established nomogram provided a better prediction of survival for GBPA patients than the traditional TNM models.
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BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs which function as novel regulators in human cancers. In this study, we aimed to investigate the functional roles and related molecular mechanisms of circ_0006282 in gastric cancer (GC) progression. METHODS: Fifty-five GC patients were enrolled in this study. GC cells (AGS and HGC-27) and normal cells (GES-1) were cultured in RPMI1640 added with 10% FBS and 1% penicillin-streptomycin. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the expression levels of circ_0006282, transcription elongation factor B subunit 1 (TCEB1) mRNA, miR-144-5p and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein ß (YWHAB; also known as 14-3-3ß). RNase R assay was used to determine the characteristic of circ_0006282. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were employed for cell proliferation. Transwell assay was conducted for cell migration and invasion. Western blot assay was carried out to measure the protein levels of Cyclin D1, matrix metalloprotein 9 (MMP9) and YWHAB. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were adopted to analyze the interaction between miR-144-5p and circ_0006282 or YWHAB. Murine xenograft model assay was performed to explore the function of circ_0006282 in vivo. RESULTS: Circ_0006282 level was increased in GC tissues and cells compared to normal tissues and cells. Silencing of circ_0006282 restrained GC cell proliferation, migration and invasion. For mechanism analysis, circ_0006282 was identified to function as the sponge for miR-144-5p to positively regulate YWHAB expression in GC cells. Moreover, miR-144-5p inhibition or YWHAB overexpression effectively reversed the impacts of circ_0006282 knockdown on GC cell growth and motility. Additionally, circ_0006282 knockdown blocked tumor growth of GC in vivo. CONCLUSION: Circ_0006282 facilitated the malignant behaviors of GC cells through circ_0006282/miR-144-5p/YWHAB axis.
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BACKGROUND: About 80% lung cancer is non-small cell lung cancer (NSCLC) and more than 70% are in advanced stage. The aim of this study is to evaluate the clinical efficacy and the side effects of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer. METHODS: Twenty-nine patients with advanced non-small cell lung cancer were treated with erlotinib 150 mg/d, then the adverse reaction and clinical efficacy were recorded during 3 months. RESULTS: Total 29 patients were evaluated for efficacy. The total rate of effect was 20.69%, including 1 case CR, 5 cases PR, 9 cases SD and 14 cases PD. We compared the effective rate of stage III with IV. There were no significant difference between the effective rate of stage III and IV (P=0.337). The main side effects were rash (37.93%), diarrhea (17.24%) and vomiting (6.9%) and most side effects were grade I and II. CONCLUSIONS: Erlotinib for elderly patients with advanced non-small cell lung cancer have better effective and less toxic effects and the further clinical study should be warranted.
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BACKGROUND: About 80% lung cancers belong to non-small cell lung cancer (NSCLC) and more than 70% are in advanced stage. The aim of this study was to evaluate the clinical efficacy and toxicity of erlotinib and GP/TP regimen on advanced non-small cell lung cancer. METHODS: Ninety-one advanced NSCLC patients with different treatments from January 2007 to April 2009 in our hospital were retrospectively analyzed. Ninety-one patients were divided into the erlotinib and TP/GP group. Erlotinib group: received erlotinib 150 mg/dl TP/GP group: the original chemotherapy for advanced non-small cell lung cancer. The cycles were repeated for 21 days. The patients were given docetaxel (80 mg/m(2), d1) or gemcitabine (1 000 mg/m(2), d1, 8) +cisplatin (70 mg/m(2), d2); then the adverse reaction and clinical efficacy were recorded during 3 months. RESULTS: Total 91 patients were evaluated for efficacy. The total rate of effect was 23.33% in erlotinib group. The side effects were erythra, diarrhea and vomiting. Pulmonary fibrosis was found in one patient after 21 days. TP/GP group: the total rate of effect was 27.78% and 28% and the side effects were bone marrow depression and reaction of gastrointestinal tract. There were no significantly difference between the two groups in the total rate of effect (P>0.05). But the side effects were less in erlotinib group, and there were significantly difference between the two groups. CONCLUSIONS: Erlotinib on advanced non-small cell lung cancer shows more effectiveness and adverse reactions are tolerable. The further clinical study should be warranted.
