BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,th...BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.展开更多
BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also re...BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes.Central nervous system(CNS)metastasis is very rare in ALK+ALCL.Patients with CNS involvement show an inferior prognosis.CASE SUMMARY Here,we present the case of an 8-year-old girl diagnosed with ALK+ALCL.She presented with fever,skin nodules,leg swelling,and abdominal pain over the preceding 6 mo.She had extensive involvement and showed an extraordinary rare translocation,t(2;17)/CLTC-ALK,as demonstrated by RNA-seq.She underwent chemotherapy as per ALCL99,followed by vinblastine(VBL)maintenance treatment,and achieved complete remission.However,she developed CNS relapse during VBL monotherapy.The patient achieved a durable second remission with high-dose chemotherapy(including methotrexate 8 g/m2)and continuous treatment with alectinib and VBL.CONCLUSION Alectinib showed significant and durable CNS effects in this patient.However,more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.展开更多
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...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 IC_(50) value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196 M with an IC_(50) 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 L1196 M, F1174 L, R1275 Q and C1156 Y.展开更多
Alectinib是一种口服间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)抑制剂,能选择性抑制ALK和转染重排(rearranged during transfection,RET)激酶。2015年12月由美国FDA加速批准上市,用于治疗ALK阳性、转移性非小细胞肺癌(NSCLC)...Alectinib是一种口服间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)抑制剂,能选择性抑制ALK和转染重排(rearranged during transfection,RET)激酶。2015年12月由美国FDA加速批准上市,用于治疗ALK阳性、转移性非小细胞肺癌(NSCLC)进展或不能耐受克唑替尼(crizotinib)治疗的患者。临床试验表明其疗效较好,主要不良反应为乏力、便秘、水肿、肌肉疼痛和咳嗽等。现对其作用机制、药动学、临床研究及不良反应等做一综述。展开更多
目的:分析阿来替尼药品不良反应(ADR)的发生情况与临床特点,为临床安全用药提供参考。方法:检索PubMed、Web of Science、CNKI和万方数据库关于阿来替尼致ADR的相关文献,对病例中患者信息、ADR发生时间、累及系统/器官、临床表现、不良...目的:分析阿来替尼药品不良反应(ADR)的发生情况与临床特点,为临床安全用药提供参考。方法:检索PubMed、Web of Science、CNKI和万方数据库关于阿来替尼致ADR的相关文献,对病例中患者信息、ADR发生时间、累及系统/器官、临床表现、不良反应分级、处理和转归等信息进行统计分析。结果:共纳入阿来替尼致ADR个案报道25篇,涉及不良反应28例,其中新的不良反应8例。患者年龄主要集中在51~80岁(71.43%);女性发生率更高(20例,71.43%);ADR多发生在用药后180 d内(24例,85.72%);以呼吸系统(9例,32.14%)、皮肤及其附件(7例,25.00%)损害较为多见;3级及以上不良反应17例(60.71%);所有患者转归良好。结论:阿来替尼相关ADR累及全身多个系统/器官,且其中不乏新的严重ADR,建议临床应关注阿来替尼致ADR的特点及处理原则,以降低用药风险。展开更多
文摘BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.
基金Supported by the Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority,No.XTZD20180204。
文摘BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes.Central nervous system(CNS)metastasis is very rare in ALK+ALCL.Patients with CNS involvement show an inferior prognosis.CASE SUMMARY Here,we present the case of an 8-year-old girl diagnosed with ALK+ALCL.She presented with fever,skin nodules,leg swelling,and abdominal pain over the preceding 6 mo.She had extensive involvement and showed an extraordinary rare translocation,t(2;17)/CLTC-ALK,as demonstrated by RNA-seq.She underwent chemotherapy as per ALCL99,followed by vinblastine(VBL)maintenance treatment,and achieved complete remission.However,she developed CNS relapse during VBL monotherapy.The patient achieved a durable second remission with high-dose chemotherapy(including methotrexate 8 g/m2)and continuous treatment with alectinib and VBL.CONCLUSION Alectinib showed significant and durable CNS effects in this patient.However,more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.
基金Financial support from National Natural Science Foundation of China (Nos. 81430080, 81125021 and 81373277)National Science & Technology Major Project on ‘Key New Drug Creation and Manufacturing Program’, China (No. 2012ZX09103-101-035)
文摘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 IC_(50) value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196 M with an IC_(50) 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 L1196 M, F1174 L, R1275 Q and C1156 Y.
文摘Alectinib是一种口服间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)抑制剂,能选择性抑制ALK和转染重排(rearranged during transfection,RET)激酶。2015年12月由美国FDA加速批准上市,用于治疗ALK阳性、转移性非小细胞肺癌(NSCLC)进展或不能耐受克唑替尼(crizotinib)治疗的患者。临床试验表明其疗效较好,主要不良反应为乏力、便秘、水肿、肌肉疼痛和咳嗽等。现对其作用机制、药动学、临床研究及不良反应等做一综述。
文摘目的:分析阿来替尼药品不良反应(ADR)的发生情况与临床特点,为临床安全用药提供参考。方法:检索PubMed、Web of Science、CNKI和万方数据库关于阿来替尼致ADR的相关文献,对病例中患者信息、ADR发生时间、累及系统/器官、临床表现、不良反应分级、处理和转归等信息进行统计分析。结果:共纳入阿来替尼致ADR个案报道25篇,涉及不良反应28例,其中新的不良反应8例。患者年龄主要集中在51~80岁(71.43%);女性发生率更高(20例,71.43%);ADR多发生在用药后180 d内(24例,85.72%);以呼吸系统(9例,32.14%)、皮肤及其附件(7例,25.00%)损害较为多见;3级及以上不良反应17例(60.71%);所有患者转归良好。结论:阿来替尼相关ADR累及全身多个系统/器官,且其中不乏新的严重ADR,建议临床应关注阿来替尼致ADR的特点及处理原则,以降低用药风险。
