Pharmaceutical care for rare ADR in a patient with ALK-positive non-small cell lung cancer induced by alectinib / 中国药房

OBJECTIVE To provide reference for safe drug use in patients with anaplastic lymphoma kinase （ALK）-positive non-small cell lung cancer （NSCLC）. METHODS Clinical pharmacists participated in the diagnosis and treatment of a patient with ALK-positive NSCLC who developed bilateral pleural effusion and hemolytic anemia after taking alectinib； regarding symptoms such as pleural effusion and hemolytic anemia in the patient， clinical pharmacists investigated the patient’s history of medication and disease， as well as potential drug interaction； to consider the correlation between the patient’s use of alectinib and the duration of pleural effusion and hemolytic anemia， clinical pharmacists suggested that clinical doctors discontinued alectinib and used reduced dose treatment after the pleural effusion improved， but the patient suffered from bilateral pleural effusion and hemolytic anemia again； after evaluating the correlation between alectinib and bilateral pleural effusion and hemolytic anemia using the Naranjo’s assessment scale， clinical pharmacists recommend permanent discontinuation of alectinib and jointly recommend replacement with ensartinib with clinical physicians. RESULTS Physicians adopted the suggestions of clinical pharmacists. The pleural effusion subsequently regressed and hemolytic anemia improved after replacing the drug. The correlation between alectinib and bilateral pleural effusion and hemolytic anemia was confirmed. CONCLUSIONS Clinical pharmacists participate in pharmaceutical monitoring of ALK-positive NSCLC patients， assist clinical doctors in developing personalized medication recommendations， and ensure the safety of patient medication.

Efficacy of alectinib for ALK-positive NSCLC brain metastases / 中国肿瘤临床

Objective: To investigate the effect of alectinib in the treatment of brain metastases from anaplastic lymphoma kinase(ALK)positive non-small cell lung cancer (NSCLC). Methods: Thirty-four cases of ALK-positive NSCLC in Tianjin Medical University Cancer Institute and Hospital, between August 2016 to October 2019, were retrospectively analyzed. Thirteen cases received first-line single drug therapy (600 mg PO bid) of Alectinib. 7 cases (53.8%) were male, 6 cases were female (46.2%), the median age was 51 (35-72). The Kaplan-Meier method was used to examine progression-free survival (PFS). Results: The median progression-free survival (mPFS) of the alectinib group was 24.5 months, and the adverse drug reactions were mild. Conclusions: The use of alectinibas first-line treatment after the local treatment of measurable intracranial lesions significantly increased the PFS of patients with brain metastases from ALK-positive NSCLC.

Literature Analysis of Adverse Drug Reactions Induced by Alectinib / 中国药房

OBJECTIVE：To explore the regularity and characteristics of adverse drug reactions （ADR）induced by alectinib ， and to provide reference for rational drug use in clinic. METHODS ：Retrieved from CNKI ，Wanfang database ，VIP，PubMed， Web of Science and Embase database during the inception to Mar. 1st，2021，case reports of alectinib-induced ADR were collected ， summarized and analyzed with descriptive statistical analysis method in terms of general information ，occurrence time of ADR ， involved organ/system ，clinical manifestations ，treatment and outcome ，etc. RESULTS ：A total of 17 literatures were included ， involving 17 patients. Among them ，4 cases（23.53％）were males ，and 13 cases（76.47％）were females. The mean age of the patients was （61.82±14.18）years old. The patients were from 5 countries/regions，among which America took the largest ratio （41.18％）. Most ADR occurred within 30 days（52.94％）after therapy. ADR mainly involved skin and its appendants （35.29％）， followed by respiratory system （23.53％），urinary system （11.76％），cardiovascular system （11.76％），gastrointestinal system （11.76％）and blood system （5.87％）；hair loss ，pancreatitis and duodenal perforation belonged to ADRs not recorded in the drug instructions. After 17 patients suffered from ADR ，2 patients still continued to use aletinib ，while 15 patients withdrew aletinib and some patients received symptomatic and supportive treatment ，and their symptoms improved. Among them ，10 patients restarted aletinib treatment after their symptoms improved ，and 8 patients did not suffered from ADR again. CONCLUSIONS ：Female patients and patients over 50 years old are more likely to suffer from ADR after using aletinib ，and most of ADR occur within 1 month after treatment. ADR involves many organs/systems ，mainly skin and its appendants. Special attention should be paid to ADR such as hair loss ，pancreatitis and duodenal perforation.

Treatment of ALK Positive Non-small Cell Lung Cancer with Alectinib: A Case Report and Literature Review / 中国肺癌杂志

Lung cancer is a malignant tumor with high incidence rate and mortality rate in China and even the whole world, of which non-small cell lung cancer accounts for about 80%. Anaplastic lymphoma kinase (ALK) gene mutation accounts for about 5%. Alectinib, ALK-tyrosine kinase inhibitor (ALK-TKI), has great performance in clinical. The early detection and treatment of adverse drug reactions can greatly improve clinical benefits. This paper reports a patient of ALK positive non-small cell lung cancer was admited to Baotou Central Hospital in April 2020. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed.
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Research progress of alectinib in the treatment of ALK-positive non-small cell lung cancer / 中国肿瘤临床

Rizotinib is a first-generation anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) and plays an important role in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC). However, as with other TKIs, resistance development can-not be avoided with crizotinib. This led to the development of second generation ALK-TKIs such as alectinib, ceritinib, and brigatinib. This article reviews the research progress on treatment of ALK-positive NSCLC with alectinib, which is one of the hotspots.

Bypass signaling pathway activation mediates resistance of EML4-ALK fusion gene positive lung cancer cell line H3122 to alectinib / 中国病理生理杂志

AIM:To detect the changes of active status of bypass signaling pathways in EML4-ALK positive lung cancer cell line H3122 treated with alectinib, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), and to explore the potential mechanisms.METHODS:EML4-ALK positive cell line H3122 was treated with increasing concentrations of alectinib or/and induced by HGF, EGF and TGF-α.The cell viability was measured by CCK-8 assay.The cell apoptosis was analyzed by flow cytometry.The protein levels and phosphorylation status of ALK, c-Met and EGFR, and the downstream molecules AKT, ERK, p-AKT and p-ERK were examined by Western blot.RESULTS:The viability of the H3122 cells was inhibited by alectinib in a dose-dependent manner after administrated for 72 h, and the IC50 value was 0.042 μmol/L.The concentration-growth curves of the H3122 cells shifted to the right after induced by HGF, EGF and TGF-α.After treatment with alectinib at 0.05 μmol/L for 48 h, the apoptotic rate of H3122 cells was (20.12±1.36)%, while the apoptotic rates of the cells in the groups of alectinib combined with HGF, EGF or TGF-α were (7.85±1.03)%, (5.60±0.79)% and (4.58±1.00)%, respectively.Those values were remarkably lower than those in alectinib single treatment group (P<0.05).Alectinib inhibited the protein levels of p-ALK and its downstream signaling pathway molecules, while HGF significantly up-regulated the protein levels of p-Met and its downstream p-AKT and p-ERK.Besides, EGF and TGF-α remarkablely up-regulated the protein levels of p-EGFR and its downstream p-AKT and p-ERK.Combined treatment with crizotinib and 17-DMAG successfully inhibited the viability of the H3122 cells even in the presence of the HGF and EGFR ligands, respectively.CONCLUSION:Bypass signaling pathways are activated by HGF, EGF and TGF-α in EML4-ALK positive lung cancer cell line H3122, which may be linked to alectinib resistance.

Research progress of Alectinib in the treatment of non-small cell lung cancer / 实用肿瘤学杂志

Recently,targeted therapy plays an important role in the treatment of non-small cell lung cancer.Crizotinib,the first generation of anaplastic lymphoma kinase( ALK) tyrosine kinase inhibitor,has been ap-proved for the treatment of ALK-rearranged NSCLC in the US since 2011.However,the crizotinib therapy is ef-fective only in the early stage of treatment.After a long time treatment,therapy resistance will follow because of the emerging second mutation of the tumor cell.In recent years,as the second generation of anaplastic lymphoma kinase tyrosine kinase inhibitor, alectinib has been approved in Japan for the treatment of ALK -rearranged NSCLC patients.Thus,research progress of Alectinib for NSCLC therapy is summarized in this article.

Alectinib: a novel second generation anaplastic lymphoma kinase (ALK) inhibitor for overcoming clinically-acquired resistance

The development of inhibitors for the tyrosine anaplastic lymphoma kinase (ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing. Although this drug offers significant clinical benefit to the ALK-positive patients, resistance has been developed through a variety of mechanisms. In addition to ceritinib, alectinib is another second-generation ALK inhibitor launched in 2014 in Japan. This drug has a unique chemical structure bearing a 5H-benzo[b]carbazol-11(6H)-one structural scaffold with an IC50 value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196M with an IC50 of 1.56 nmol/L. In the clinic, alectinib is highly efficacious in treatment of ALK-positive non-small cell lung cancer (NSCLC), and retains potency to combat crizotinib-resistant ALK mutations L1196M, F1174L, R1275Q and C1156Y.