抗肿瘤血管生成靶向药物的不良反应、发生机制及处理

通过抑制新生血管以达到控制肿瘤是目前抗肿瘤治疗的重要研究方向,抗肿瘤血管生成靶向药物在临床肿瘤治疗中已广泛应用,包括贝伐单抗、重组人血管内皮抑素以及多靶点激酶抑制剂索拉非尼、舒尼替尼等,药物不良反应包括高血压、心脏毒性、血栓形成、出血、蛋白尿、胃肠道穿孔、伤口愈合不良以及索拉非尼和舒尼替尼较常见的疲乏、腹泻、手足综合征等,多数不良反应为1及或2级,患者耐受性及依从性较好.     

抗肿瘤血管生成靶向药物的不良反应、发生机制及处理

通过抑制新生血管以达到控制肿瘤是目前抗肿瘤治疗的重要研究方向,抗肿瘤血管生成靶向药物在临床肿瘤治疗中已广泛应用,包括贝伐单抗、重组人血管内皮抑素以及多靶点激酶抑制剂索拉非尼、舒尼替尼等,药物不良反应包括高血压、心脏毒性、血栓形成、出血、蛋白尿、胃肠道穿孔、伤口愈合不良以及索拉非尼和舒尼替尼较常见的疲乏、腹泻、手足综合征等,多数不良反应为1及或2级,患者耐受性及依从性较好.     

抗肿瘤血管生成靶向药物的不良反应、发生机制及处理

通过抑制新生血管以达到控制肿瘤是目前抗肿瘤治疗的重要研究方向,抗肿瘤血管生成靶向药物在临床肿瘤治疗中已广泛应用,包括贝伐单抗、重组人血管内皮抑素以及多靶点激酶抑制剂索拉非尼、舒尼替尼等,药物不良反应包括高血压、心脏毒性、血栓形成、出血、蛋白尿、胃肠道穿孔、伤口愈合不良以及索拉非尼和舒尼替尼较常见的疲乏、腹泻、手足综合征等,多数不良反应为1及或2级,患者耐受性及依从性较好.     

肝癌患者口服甲磺酸仑伐替尼不良反应护理

本个案针对中国医学科学院北京协和医学院肿瘤医院深圳医院2020年2月14日收治的1例肝癌口服靶向药(甲磺酸仑伐替尼)引起肛周瘙痒和多处皮损的病例进行分析。患者带肛周皮损入院,与压疮区别后,判断为肝癌患者口服甲磺酸仑伐替尼所致药物不良反应,对症给予治疗与护理。伤口明显好转后,患者出院。此案为新发现的甲磺酸仑伐替尼说明书上没有载出的药物不良反应,为临床口服靶向药患者药物不良反应医疗护理工作提供参考。     

伊马替尼治疗胃肠道间质瘤的心脏毒性及其机制的研究进展

酪氨酸激酶抑制剂伊马替尼是治疗胃肠道间质瘤（gastrointestinal stromal tumor, GIST）的主要药物之一,然而部分患者服用伊马替尼后会出现严重的心脏毒性,其发生机制尚不十分清楚。目前研究认为,内质网应激介导的不同信号转导通路在伊马替尼致心脏毒性中发挥了重要作用,而这些信号通路又通过c-Abl与线粒体信号通路发生作用。伊马替尼竞争性结合酪氨酸激酶区ATP结合位点,引起心肌细胞能量代谢异常,增加了氧化应激,使c-Abl表达及PDGFR磷酸化异常,而c-Abl和PDGFR介导的信号转导通路异常与伊马替尼心脏毒性的发生密切相关。     

基于真实世界医药数据库的PD-1/PD-L1抑制剂相关不良反应信号挖掘

目的 利用真实世界中的医药大数据，挖掘肿瘤免疫治疗药物程序性死亡受体1/程序性死亡配体1(PD-1/PD-L1)抑制剂发生不良反应的风险信号，促进此类药物在临床安全合理使用。方法 收集美国食品与药品监督管理局(FDA)不良反应数据库中2014年9月1日至2022年9月30日的不良反应报告。经过数据标准化处理，使用报告比值比(ROR)法及数据交叉对比分析，对PD-1/PD-L1抑制剂的不良反应信号进行数据挖掘。结果 获得PD-1/PD-L1抑制剂的不良反应报告106 946份。经数据挖掘，有显著意义的不良反应风险信号2741个，其中帕博利珠单抗886个、纳武利尤单抗956个、阿替利珠单抗545个、度伐利尤单抗255个、阿维鲁单抗99个。全部风险信号共累及25个系统或器官，主要为神经系统疾病、胃肠系统疾病、感染类疾病等。报告数前20位的不良反应中未在说明书中出现的信号有22个。所有PD-1/PD-L1抑制剂均存在的风险信号包括自身免疫性结肠炎、肿瘤溶解综合征、血肌酸磷酸激酶升高、心肌病等。结论 临床使用PD-1/PD-L1抑制剂时，应关注患者的神经系统功能、胃肠道症状以及可能出现的感染，根...     

信迪利单抗联合安罗替尼治疗三线及以上肺腺癌患者的临床疗效

目的:观察信迪利单抗联合安罗替尼用于治疗三线及以上晚期肺腺癌的临床疗效和不良反应。方法:将自2019年3月至2020年8月在本院肿瘤科进行诊治的118例晚期肺腺癌患者分为安罗替尼组（n=59）和联合治疗组（n=59）,分别采用安罗替尼单药,信迪利单抗联合安罗替尼进行治疗,采用胸部计算机断层扫描放射,计算机断层扫描,骨扫描等检测患者肿瘤进展,治疗前后采用TDL生命质量测定表(TDL-QOLAS)反映患者生命质量水平,通过酶联免疫吸附法测量血液肿瘤标志物水平,此外,在随访截至时使用Morisky药物依从性量表评估所有患者服药依从性,通过Kaplan-Meier曲线描述两组患者的PFS（无病进展期）和OS（总生存期）,并观察用药期间两组患者不良反应发生情况。结果:联合治疗组的ORR、PFS和OS均明显高于安罗替尼组,分别为23.7% vs 10.2%、6.9个月vs 4.7个月、15.7个月vs 9.3个月,差异有统计学意义（P＜0.05）。血液学分析显示,联合治疗与安罗替尼单用均可显著降低血清肿瘤标志物水平,而联合治疗效果更佳（P＜0.05）,此外,相较于安罗替尼单药组,联合治疗可以更好的提高患者生活质量并具有良好的用药依从性（P＜0.05）,且联合治疗组未明显增加治疗相关不良反应,未发生因不良反应终止治疗的事件,无治疗相关死亡事件。结论:信迪利单抗联合安罗替尼治疗三线及以上肺腺癌患者,可显著改善患者的生存时间,具有良好的用药依从性和安全性,值得临床进一步推广。     

伊布替尼的常见不良反应及临床应对策略

伊布替尼作为第一代布鲁顿酪氨酸激酶(Bruton's tyrosine kinase，BTK)抑制剂，为治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(chronic lymphocytic leukemia/small lymphocytic lymphoma，CLL/SLL)、复发的套细胞淋巴瘤(mantle cell lymphoma，MCL)等在内的B细胞淋巴瘤有效率高、安全性好的口服小分子靶向药物。自伊布替尼在国内上市以来，越来越多的中国患者从中获益，但随着使用例数增多和时间延长，临床上面临着更多与既往化疗药物相比出现的特殊不良反应，如出血、房颤、腹泻和关节痛等。因伊布替尼作用机制的独特性，在处理不良反应时亦需关注药物相互作用。本文总结相关文献中伊布替尼不良反应的处理策略，旨在为临床提供参考。      

阿帕替尼治疗恶性肿瘤的临床研究进展

随着抗血管生成靶向治疗的发展,作用于血管内皮生长因子（vascular endothelial growth factor,VEGF）及其血管内皮生长因子受体（vascular endothelial growth factor receptor ,VEGFR）信号通路的抗肿瘤药物越来越受到广泛的关注。血管内皮细胞生长因子受体- 2（vascular endothelial growth factor receptor 2,VEGFR- 2）抑制剂阿帕替尼是一种高效抗血管生成药物,是最新上市的口服分子靶向抗肿瘤药物之一。阿帕替尼在人体生物利用度高,安全性及耐受性良好。上市前后一系列大规模的随机、对照临床试验证实阿帕替尼在多种恶性肿瘤中具有一定的客观有效率和生存获益,如胃癌、非小细胞肺癌（non-small cell lung cancer ,NSCLC ）、乳腺癌等,尤其是在胃癌中。2014年该药在中国批准上市应用于临床治疗晚期胃癌。目前正在进行胃癌、肺癌、肝癌、食管癌、结直肠癌等多种恶性肿瘤的Ⅱ/ Ⅲ期临床试验,以探讨其单独或联合抗肿瘤活性。本文就阿帕替尼抗肿瘤机制、对不同类型肿瘤的临床疗效、安全性及不良反应、药物相互作用、耐药及生物标志物等最新研究进展进行综述,以加深对该药抗肿瘤应用的了解,为临床实践提供参考,并期望为恶性肿瘤患者的治疗带来一些新的选择。      

甲磺酸阿帕替尼治疗晚期胃癌的疗效及安全性分析

目的 探讨甲磺酸阿帕替尼治疗晚期胃癌的临床疗效及安全性.方法 回顾性分析接受甲磺酸阿帕替尼治疗的晚期胃癌患者28例,既往均接受过二线及二线以上治疗.14例患者作为对照组接受甲磺酸阿帕替尼模拟片,14例患者作为观察组接受甲磺酸阿帕替尼片,剂量均为850 mg,1次/天,早餐后服用.采用RECIST、NCI以及CTC标准对比分析2组患者治疗疗效以及药物不良反应.结果 观察组患者PR、SD、PD、RR以及DCR显著优于对照组,差异具统计学意义(P＜0.05);但2组患者OS和PFS相比较,差异不具统计学意义(P＞0.05).观察组中AFP阳性胃癌患者OS和PFS显著高于AFP阴性胃癌患者,差异具统计学意义(P＜0.05).甲磺酸阿帕替尼主要不良反应表现为骨髓抑制等血液毒性和手足综合征等非血液毒性,其中高血压发生率为64.3％、骨髓抑制发生率为78.6％,不良反应发生多为Ⅰ～Ⅱ级,无Ⅳ级不良反应发生.结论 甲磺酸阿帕替尼治疗晚期胃癌,疗效确切,不良反应患者可耐受,可推广使用.     

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study, we aimed to determine the incidence of adverse drug reactions (ADRs) of atezolizumab, identify ADR signals that are significantly related to atezolizumab, and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events (ADEs) reported in the American Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Methods In total, 4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed. Results The top three ADEs were febrile neutropenia (3.7％), anemia (2.9％), and acute renal failure (2.3％). In addition, the incidence rates of some ADEs were significantly different according to sex and age. The systematic organ classification of atezolizumab ADEs involved 32 systems, among which the top three were blood and lymphatic system disorders (585 cases, 12.2％), gastrointestinal disorders (433 cases, 9.0％), and infections and infestations (401 cases, 8.4％). The reporting odds ratio (ROR) method was used to detect the ADR signals of atezolizumab. The ROR (95％ confidence interval) of the top ADE, febrile neutropenia, was 39.236 (33.757–45.604). In addition, we found 121 cases of complications associated with immune-related ADEs. Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use, suggesting that atezolizumab has an acceptable and controllable drug effect.     

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis

Immune checkpoint inhibitors (ICIs) combined with the anti-angiogenesis drug bevacizumab is one of the future directions of immunotherapy. However, the potential adverse drug reactions (ADRs) caused by combination therapy remain unclear. Current research on ADRs of combination therapy in cancer patients is extremely limited. Our study aims to help determine the safety of combination therapy. We downloaded the ADR reports on combination therapy, from the first quarter of 2012 to the fourth quarter of 2021, from the FDA adverse event reporting system (FAERS) database and conducted a large-scale retrospective study. The ADR signals were monitored by reporting odds ratio (ROR) and analyzing the risk of different ADRs in patients with Pan-cancer. A total of 2094 cases were selected, after excluding duplicate data and the use of chemotherapy drugs. We evaluated the risk of ADR in Pan-cancer patients. Combination therapy was an independent risk factor for adverse drug reactions associated with interstitial lung disease (OR: 8.62; 95% CI: 6.14-12.10, P < .0001), hypertension (OR: 1.35; 95% CI: 1.11-1.65, P < .01) and gastrointestinal bleeding (OR: 3.16; 95% CI: 2.21-4.51, P < .0001). A subgroup analysis revealed that the risk of endocrine system-related ADRs was elevated in patients receiving different combination therapies or with certain tumor types. We retrospectively studied the ADR of combination therapy in Pan-cancer patients and analyzed the distribution characteristics of ADR from the perspectives of treatment strategy and cancer types to provide recommendations for the individualized management of patients receiving combination therapy.     

索拉非尼不良反应３６例的分析与处理

目的：回顾性分析肾癌和肝胆癌患者在服用索拉非尼治疗过程中不良反应的出现频率、治疗及护理方法等,总结经验,指导临床。方法：对使用索拉非尼出现不良反应的３６例晚期肝癌和肾癌患者进行常规护理及心理护理,观察服药期间出现的各种症状并及时处理,对各种可能与索拉非尼有关的不良反应进行分级、记录与统计分析。结果：３６例患者中除１例患者因心肌梗死死亡,１例患者因Ⅲ度皮肤不良反应而停药外,其余３４例均能够继续接受索拉非尼。其中皮疹、疼痛及腹泻为常见不良反应,且分级多为Ⅰ度和Ⅱ度,Ⅲ度不良反应的发生率为１９.４％。结论：索拉非尼合并皮疹及腹泻等轻中度不良反应的发生率较高,亦有心肌梗死的严重不良反应发生。常规护理、心理护理和积极治疗将有助于减轻不良反应。     

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review

BackgroundRuxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS).Materials and MethodsThis is a retrospective study utilizing FAERS, a pharmacovigilance database. We queried FAERS for cases of MTB and AMI secondary to ruxolitinib between January 1, 2011 and December 31, 2018. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). ROR was considered significant when the lower limit of 95% confidence interval (CI) was > 1.ResultsThere were 91 reported cases of MTB associated with ruxolitinib compared with 4575 cases from all other drugs. The ROR was significant at 9.2 (95% CI, 7.5-11.4). There were 23 reports of AMI with ruxolitinib compared with 1287 reported with all other drugs. The ROR was significant at 8.3 (95% CI, 5.5-12.6). Twelve (13.2%) patients with MTB and 8 (34.8%) with AMI died.ConclusionPatients on ruxolitinib are at increased risk of developing MTB and AMI. Clinicians should be aware of this risk and consider screening patients for latent MTB prior to initiating ruxolitinib.     

143例肿瘤患者应用抗肿瘤药物不良反应临床分析

目的探讨肿瘤患者应用抗肿瘤药物不良反应发生的规律及特点。方法以143例肿瘤患者为研究对象,对其抗肿瘤药物应用的各项不良反应。结果不良反应发生以老年人多见,多发生于用药24h内。给药途径以静脉滴注及注射更易发生不良反应,抗肿瘤药造成的不良反应最多,紫杉醇、奥沙利铂、氟尿嘧啶、高聚生及巴曲亭更容易产生严重不良反应。联合用药中,单联及二联用药最易产生不良反应。结论临床中需加强对抗肿瘤药物不良反应的预防及监测。     

Cardiac effects of cytokines produced after rituximab infusion

Rituximab (Mabthera) is used in the treatment of refractory low-grade non-Hodgkin's lymphoma or in case of relapse after chemotherapy. Among the different adverse reactions with this drug, the most common is a constellation of symptoms (fever, rigors and chills) that occur more frequently during administration of the first dose of drug. These symptoms could be related to a cytokine-release syndrome. We report the case of a 46 year-old patient, presenting a familial cardiomyopathy, deceased a few minutes after having developed this syndrome, at the time of the 2nd infusion of rituximab. Several hypothesis have been suggested to explain this sudden death: a cardiac failure following deterioration of the systolic function, potentially related to the negative inotropic effects of TNFalpha, and/or an impairment of the diastolic function following the volemic overload. The impact of the reflex "administration of monoclonal antibody/cytokine-release syndrome" was only little investigated under physiologic or pathologic conditions. In spite of a risk of adverse reactions apparently moderated compared to the other drugs used in this context, this case report underlines the need for a special attention when using rituximab among patients with cardiac risk factors (reassessment of the benefit-risk ratio, specific monitoring, pre medication). More generally, it underlines the need for a systematic and continuous identification and reporting of adverse drug reactions to the French network of regional pharmacovigilance centres.     

Development of clinical pathway in S-1 chemotherapy for gastric cancer

We have developed a clinical pathway to enable the safe continuous administration of S-1 (TS-1^®) in ambulatory care for patients with advanced gastric cancer. The S-1 clinical pathway includes a pathway for clinicians, a pathway for patients, and such assist tools as a medication diary, an explanatory document containing instructions relating to patient compliance, a table of associations between adverse reactions and prodromes, and general principles for dose reduction and withdrawal. These pathways and assist tools will improve the patient's perception of adverse reactions, thereby contributing to early discovery and rapid action against adverse events. The S-1 clinical pathway has been used with ten patients. S-1 administration has been continued in seven patients. In four of the seven patients, continued administration on the occurrence of adverse reactions was made possible by the use of appropriate measures such as drug withdrawal or dose reduction. It was confirmed that the S-1 clinical pathway was a useful tool for cancer chemotherapy in ambulatory care.     

大剂量甲氨蝶呤化疗后延迟排泄的影响因素和发生机制的研究进展

本文从患者生理状态、药物相互作用、代谢酶和转运体等方面,探讨大剂量甲氨蝶呤化疗后延迟排泄的影响因素和发生机制,探究如何减少大剂量甲氨碟呤（HD-MTX）治疗恶性肿瘤延迟排泄的发生,为随后的研究奠定基础。通过总结文献,得出甲氨喋呤延迟排泄的因素需综合判断生理因素、药物相互作用、代谢酶等多方面的结论,在保证治疗有效性的基础上进行常规解救,并结合以上因素进行个体化用药,以减少不良反应。     

Immune-related adverse events in older adults: Data mining of the FDA Adverse Event Reporting System

IntroductionRecent studies reveal that there is no difference in the efficacy of immune checkpoint inhibitors (ICIs) between younger adults and older adults. However, it remains unclear whether age is a risk factor for immune-related adverse events (irAEs).Materials and methodsTo analyze the association between irAEs and age based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and December 2020, we performed a case/noncase study on ICI-related adverse events. Cases were defined as adverse event cases with ICI therapy and irAEs, and noncases were defined as adverse event cases with ICI therapy and without irAEs. One case was matched to a noncase using the sex, reporter, report year, and type of ICI regimen. The reporting odds ratios (RORs) were used to assess the disproportionality of irAEs between older adults (≥65 years) and younger adults (<65 years).ResultsThe study shows that compared with younger adults, the ROR of older adults was 1.12 (95% confidence interval [CI]: 1.08–1.16) and 1.18 (95% CI: 1.14–1.23) before and after matching, respectively. The signal of age-related irAEs was detected in patients treated with ICI monotherapy but not in patients treated with combination therapy. Further analysis revealed a spectrum of age-related toxicities including cardiovascular toxicities, lung toxicities, musculoskeletal toxicities, nervous system toxicities, renal toxicities, and skin toxicities.ConclusionIn this analysis performed based on the FAERS, irAE cases were more likely to be reported in older adults. Our pharmacovigilance study complements the safety data of clinical trials. Further studies are expected to explore the underlying reasons for irAEs in older adults.     

Management of pharmacists on the cancer chemotherapy

The duties of hospital pharmacists include drug dispensing, drug management, preparation of injections, drug information provision, in-hospital preparation, drug management guidance (centering on patient compliance instructions), tests and research, and education. The Department of Pharmacy conducts most of these activities, which are not noticed by other medical staff. As members of medical care teams, pharmacists must share information and perform their jobs from a pharmaceutical viewpoint in order to fulfill their duties as drug specialists, which include management of patient conditions, patient-oriented patient compliance instructions, risk management, management of dosages and administration methods for anticancer drugs during cancer chemotherapy, discovery of the initial symptoms of adverse drug reactions and prevention of adverse drug reactions to obtain the optimum effect, education on self-care after discharge from the hospital, and evaluation of drug economics for cancer chemotherapy. It is important that they acquire sophisticated expertise and stay in as close contact as possible with patients and their families.