BACKGROUND: Microsatellite stable (MSS) colorectal cancer (CRC) is a common type of tumor with limited treatment options. Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.
OBJECTIVE: To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment.
METHODS: During the period spanning from April 2019 to April 2022, Zhejiang Provincial People\'s Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study, the observation group and the control group. The control group was administered anlotinib hydrochloride as their designated therapy, whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group. The administration of treatment occurred in cycles consisting of a duration of 3 wk, and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups. A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period. Changes in the levels of carcinoembryonic antigen, carbohydrate antigen 199 (CA199), CA125, and T cell subsets (CD4+, CD8+, CD4+/CD8+) as well as the assessment of the quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy. Finally, a 1-year follow-up was conducted for both groups of patients, and the survival status was recorded and analyzed.
RESULTS: The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group, with a statistically significant discrepancy (76.09% vs 50.00%), reaching a significance level denoted as P < 0.05. Following the administration of treatment, the observation group manifested a considerable reduction in numerous serum indicators, which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Post-treatment, the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration, surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Subsequent to the therapeutic intervention, the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality. These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group (P < 0.05). The safety levels of drug use in the two group were comparable (19.57% vs 13.04%), and no distinct difference was observed upon comparison (P > 0.05). After the completion of treatment, both groups of patients underwent a 1-year follow-up outside the hospital. Throughout this period, 1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up. During the follow-up period of the observation group, 12 patients died, resulting in a survival rate of 73.33% (33/45), while in the control group, 21 patients died, resulting in a survival rate of 52.27% (23/44). The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups (log-rank = 4.710, P = 0.030).
CONCLUSIONS: The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients, leading to improvements in patient immunity and prognosis. Additionally, it exerted inhibitory effects on the expression of carcinoembryonic antigen, CA199, and CA125.

UNASSIGNED: Half of the population of non-small cell lung cancer (NSCLC) patients are older than 70 years and have limited therapeutic options due to poor tolerance and being excluded in most clinical trials. Anlotinib hydrochloride, a novel oral multi-target tyrosine kinase inhibitor, has been approved for the standard third-line treatment for NSCLC in China. Herein we report an elderly NSCLC patient without any driver gene mutations who was undergoing anlotinib as a front-line treatment and who achieved long-term survival.
UNASSIGNED: The 77-year-old male patient was admitted to the hospital for chest tightness after engaging in physical activity for a week. The patient has been diagnosed with stage IIIB driver gene-negative squamous cell lung carcinoma. After that, he was treated with anlotinib for 2 years and 10 months from the first diagnosis until the last disease progression. Briefly, anlotinib combined with platinum-based chemotherapy was performed as the first-line therapy over six cycles. After 6 more cycles of anlotinib monotherapy maintenance, disease progression occurred. Then, anlotinib combined with tegafur was administered as a salvage treatment, and the disease was controlled again. After 29 cycles of anlotinib combined with tegafur regimens, the disease progressed finally. The patient achieved a total of 34 months of progression-free survival after anlotinib was used as the front-line treatment. He is still alive with a good performance status now (performance status score: 1).
UNASSIGNED: This patient achieved long-term survival using anlotinib as a front-line regimen combined with chemotherapy.

UNASSIGNED: Both anlotinib and programmed death 1 (PD-1) monoclonal antibody (mAb) have been approved for the third line treatment of metastatic non-small cell lung cancer (NSCLC). However, the combination of these two standard therapies has not been investigated in third-line or further-line treatment of patients with advanced NSCLC.
UNASSIGNED: We reviewed 22 patients with NSCLC who received anlotinib combined with PD-1 mAb therapy from July 2018 to October 2019 at Sir Run Run Shaw Hospital. Based on the baseline characteristics, PD-L1 expression and EGFR mutation status, we retrospectively analyzed the efficacy and safety of this combination therapy by RESIST 1.1 and CTCAE 5.0.
UNASSIGNED: The combination treatment of anlotinib and PD-1 mAb in 22 NSCLC patients gained a median PFS of 6.8 months and a median OS of 17.3 months. The disease control rate (DCR) was 90.9%, and the objective response rate (ORR) was 36.4%, where 1 (4.6%) patient achieved complete response (CR) and 7 (31.8%) patients achieved partial response (PR). The median time to response was 3.9 months, and the median duration of the response was 6.8 months. The common grades 1-2 adverse events were fatigue 10/22 (45.5%), decreased appetite 9/22 (40.9%), hypertension 10/22 (45.5%); the common grades 3-4 adverse events were hypertension 2/22 (9.1%) and mouth ulceration 2/22 (9.1%).
UNASSIGNED: Anlotinib combined with PD-1 mAb showed promising efficacy in third-line or further-line treatment of NSCLC, and its adverse effects is tolerable.

Anlotinib hydrochloride is the only anti-angiogenic, multi-targeted tyrosine kinase inhibitor, which has been approved for non-small cell lung cancer and small cell lung cancer in China. In order to provide guidance for clinical practitioners to use anlotinib hydrochloride safely and efficiently, the Chinese Association for Clinical Oncologists, the Expert Committee of Vascular Targeted Therapy of Chinese Society of Clincal Oncology and the Cancer Targeted Therapy Professional Committee of China Anti-Cancer Association co-organized experts and integrated multiple evidences of Anlotinib Hydrochloride, from both clinical trial, post-marketed clinical data and the associated experiences of experts accumulated in clinical practice, etc. The present consensus covers the clinical data of anlotinib hydrochloride applied in advanced non-small cell lung cancer and small cell lung cancer, and the safety management recommendations.
盐酸安罗替尼是目前国内唯一获批治疗晚期非小细胞肺癌(NSCLC)和晚期小细胞肺癌(SCLC)的抗血管生成多靶点小分子酪氨酸激酶抑制剂。为了更好地指导临床合理、有效、安全地使用盐酸安罗替尼治疗晚期肺癌，给医师提供基于循证医学研究结果的用药建议和参考，中国医师协会肿瘤医师分会、中国临床肿瘤学会血管靶向治疗专家委员会和中国抗癌协会肿瘤靶向治疗专业委员会共同组织专家，整合了盐酸安罗替尼多项临床试验结果、临床应用的安全性数据以及专家临床实践经验，共同制定了本共识。共识的内容覆盖盐酸安罗替尼在NSCLC和SCLC中的使用及安全性管理建议等。.

Anlotinib hydrochloride is a multi-target tyrosine kinase inhibitor, which has been recently approved for the treatment of advanced non-small cell lung cancer in China. One of its mechanisms of action is the inhibition of angiogenesis and it is similar to other anti-angiogenesis drugs, as it has cardiovascular toxicity, which may damage vascular endothelial cells and result in hypertension and hyperlipidemia. All of the aforementioned factors are considered risk factors for coronary heart disease; however, the risk of developing acute myocardial infarction (AMI) has not been assessed by any previous clinical trials and subsequent research. The present case study, to the best of our knowledge, was the first to report on a patient who developed hypertension, hyperlipidemia and angina pectoris, and eventually experienced AMI, following treatment with anlotinib. This indicates that patients receiving anlotinib may require further observation and monitoring during use.

Objective: To retrospectively analyze the clinical efficacy, safety and the main factors affecting the prognosis of anlotinib hydrochloride in the treatment of advanced primary liver cancer. Methods: Fifty-five cases with advanced primary liver cancer who received anlotinib hydrochloride were enrolled. The baseline data of the patients, such as prothrombin time, total bilirubin, albumin, Child-Pugh score, procalcitonin, alpha fetoprotein, extrahepatic metastasis, cirrhosis, portal hypertension, whether or not combined surgery, pathological staging, etc before treatment were recorded. Hematological and imaging results of the patients were reviewed. Adverse events that appeared in patients at any time until the end of follow-up or loss- to- follow-up or death were recorded. The survival curve was plotted by Kaplan-Meier method, and the difference of survival time between groups was examined by log-rank test. Cox regression model of single and multiple factor were used to analyze the factors affecting the prognosis. Results: As of the last follow-up, 2 patients were lost-to-follow-up, 30 died, and 23 survived. The median survival time was 6.5 months (196 days). Grade 3 or higher adverse events included hypertension (12.73%), leukopenia (3.64%), absolute neutropenia (1.82%), thrombocytopenia (9.09%), fatigue (3.64%), anemia (1.82%), and diarrhea (1.82%). Adverse events were effectively controlled. One case had fatal ruptured esophageal varices, which were not medically related. Multivariate Cox regression analysis showed that total bilirubin (HR = 0.247, P = 0.003), albumin (HR = 0.279, P = 0.003) and procalcitonin (HR = 0.105, P = 0.012) were independent factors affecting the prognosis of advanced HCC. Conclusion: Anlotinib hydrochloride therapy is safe, effective and well tolerated in patients with advanced liver cancer, and total bilirubin, albumin, and procalcitonin are independent factors that affect the prognosis of patients with advanced liver cancer.
目的： 回顾性分析盐酸安罗替尼治疗晚期原发性肝癌的临床疗效、安全性，探索影响预后的主要因素。 方法： 纳入55例接受盐酸安罗替尼治疗的晚期原发性肝癌患者。记录患者治疗前的基线资料，如凝血酶原时间、总胆红素、白蛋白、Child-Pugh评分、降钙素原、甲胎蛋白、肝外转移、肝硬化、门静脉高压、是否联合手术、病理类型等，记录患者的血液学及影像学复查结果，随时记录患者出现的不良反应，直至患者随访截止或失访或死亡。采用Kaplan-Meier法绘制生存曲线，并使用Log-rank检验比较组间生存期差异；采用Cox单因素及多因素回归模型分析预后影响因素。 结果： 截至末次随访，2例患者失访、30例死亡、23例生存，中位生存时间6.5个月（196 d）；3级以上不良事件有高血压(12.73%)、白细胞计数降低(3.64%)、中性粒细胞绝对值降低(1.82%）、血小板计数降低（9.09%）、乏力（3.64%）、血红蛋白降低（1.82%）、腹泻（1.82%）等；不良反应都能得到有效控制；1例患者出现致死性食管静脉曲张破裂出血，为非药物相关性。多因素Cox回归分析证明总胆红素（HR = 0.247、P = 0.003）、白蛋白（HR = 0.279、P = 0.003）、降钙素原（HR = 0.105、P = 0.012）是影响晚期肝癌预后的独立因素。 结论： 盐酸安罗替尼治疗晚期肝癌患者安全有效，耐受性良好；总胆红素、白蛋白、降钙素原是影响晚期肝癌患者预后的独立因素。.

Anlotinib is a novel oral multi-targeted receptor tyrosine kinase inhibitor, which selectively inhibits VEGFR2/3, FGFR1-4, PDGFR α/β, c-kit, and Ret. It shows antitumor effect in patients with advanced refractory solid tumors. The detailed absorption, metabolism, and excretion pathways of anlotinib have not yet been fully investigated.
Six male patients were enrolled and divided into two groups. Group A (containing two patients) received 14.15 mg/80 µCi/subject [14C]-anlotinib hydrochloride. Group B (containing four patients) received 14.15 mg/120 µCi/subject [14C]-anlotinib hydrochloride. The blood, urine, and feces of all the six patients after orally administration of [14C]-anlotinib were collected. The absorption, metabolism, and excretion of [14C]-anlotinib were investigated, and the efficacy and safety of anlotinib were evaluated.
In plasma, the average time to peak concentration (Tmax) of total radioactivity was 4.42 h and the average peak concentration (Cmax) of total radioactivity was 18.80 ng Eq./g. The average values of AUC0-last, AUC0-∞, and MRT0-t were 4071 h.ng Eq./g, 13,555 h.ng Eq./g, and 125 h, respectively. The average recovery of total radioactivity (TRA) in urine and feces was 62.03%, accounting for 48.52% and 13.51% in feces and urine of the total dosage, respectively. The parent drug, a carboxylic metabolite (M30), and mono-oxidation products (M46/M66) were major drug-related components in human plasma. Oxidative metabolism played the major role in drug clearance in human. The major metabolic pathways include oxidative deamination to M2, mono-oxidation to M1, and the formation of M30. Adverse events occurred in five patients and severe adverse events (SAE) occurred in one. Tumor response were evaluated as stable disease (SD) in three, partial response (PR) in one, and progressive disease (PD) in one of the patients, respectively.
Anlotinib had a good pharmacokinetic profile with rapid absorption, long half-life, and extensive hepatic metabolism. The adverse events and efficacy were as expected.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare malignant tumor defined by a unique chromosomal translocation of the NUT gene on chromosome 15q14. This very rare tumor is usually located in midline structures, especially in the head and neck region. However, there have been no previous reports of NMC arising from the eyes. Here, we first describe a case of NMC originating in the right orbit of a 60-year-old woman. A multimodality approach, including surgery, chemotherapy, radiotherapy, and target therapy, was adopted in clinical practice.