Hyperesthesia

点击蓝字，关注我们 编者按：抗体偶联药物（ADC）是目前乳腺癌领域最前沿的研究热点之一，既有靶向药物精准锚定肿瘤细胞的作用，又有化疗的强效抗肿瘤作用。ADC从基础的药物设计上保障了对乳腺癌治疗的疗效和安全性，并为更多乳腺癌患者带来了新的治疗选择。然而，与所有抗肿瘤药物相似的是，在ADC药物临床应用过程中也会出现相关不良反应。加强对不良反应的有效管理，最大限度地发挥出药物的临床效力，对临床医生和患者而言十分重要，也影响着患者的生存转归。下面我们就一起来了解下ADC类药物的常见毒性和应对措施。 ADC药物常见不良反应 ADC通常耐受良好，但也存在一些可预测的不良反应，以及需要仔细处理的医学问题，应做到早期发现、精准评估、及时干预。 由于抗体和细胞毒性药物不同，不同 ADC 药物的不良反应也不同，需要特别关注的不良反应按照影响器官组织分类为血液学不良反应、输注相关反应、神经不良反应、肝不良反应、肺不良反应、消化系统疾病、心脏不良反应、感染、皮肤和皮下组织疾病、肿瘤溶解综合征、代谢性不良反应、眼部疾病和中枢神经不良反应等。 临床医生在用药期间应密切监测相应的不良反应，对可能产生严重后果的不良反应进行积极预防或给予支持治疗；在疑似发生不良症状时密切关注并及时诊断，确定发生不良反应后给予对应处置方案，同时调整药物治疗方案，进行延期治疗或减量处理，严重不良反应要及时停药；对于难以处理的不良反应及时开展多学科会诊，探讨解决方案。 ADC药物常见不良反应的应对措施 ADC药物常见的不良反应包括血液学不良反应、输液反应、消化道反应、周围神经病变、肝、肺和心脏毒性等。 （1）血液学不良反应 血液学不良反应是ADC药物常见的不良反应，包括全血细胞减少、中性粒细胞减少症、血小板减少症等，严重的血液学不良反应可进一步增加出血和感染的风险。 应对措施：在应用ADC药物前应进行全面血检，对于不符合治疗要求的患者应慎重用药，待血液指标恢复正常方可用药。在治疗期间也应定期监测血细胞计数，同时考虑预防性用药避免血液不良反应。 （2）输液反应 输液反应是ADC药物治疗患者常见的不良反应，发生率为2.5%～13.0%。主要症状包括发热、寒战、头疼、恶心、呕吐、疼痛、呼吸困难等。 应对措施：对有相关风险的患者，可使用预处理药物，以最大限度降低输液反应风险。在输注过程中和输注结束至少1 h内监测是否有输液反应发生。对于出现输液反应的患者，及时中断输注，并给予类固醇激素或抗组胺药对症治疗；对于发生严重输液反应的患者，建议永久停药。 （3）消化道不良反应 消化道反应是ADC药物常见的不良反应，包括恶心、呕吐和腹泻等。 应对措施：消化道反应通常为轻度，可予止吐、止泻等对症处理。反应严重者应停止用药，如症状缓解，可考虑继续用药，同时考虑预防性用药。如反复多次发生 ≥ 3级消化道反应，则应考虑停止治疗。 （4）周围神经病变 周围神经病变的症状主要表现为感觉神经损伤，如各种感觉减退、感觉过敏、感觉倒错和烧灼性疼痛等各种神经痛的症状，严重者可出现四肢无力、蹲起困难、无法行走，甚至卧床。周围神经病变的发生率不同报道有所差异（13%-62%），但以1~2级周围神经病变为主。 应对措施：当患者出现周围神经病变时，可给予B族维生素营养神经治疗；对于神经痛的症状，可选择加巴喷丁、普瑞巴林、阿米替林、文拉法辛或度洛西汀等对症治疗。 （5）肝毒性 肝毒性主要表现为ALT、AST、胆红素等的异常。 应对措施：治疗过程中应常规给患者进行肝功能检查，若出现异常，应及时护肝治疗，若有严重或致死性静脉阻塞性肝病（VOD），则立即停止用药。 （6）肺毒性 在ADC药物治疗过程中，如果患者出现呼吸困难、咳嗽、咯血，需警惕是否存在间质性肺疾病。同时密切关注患者其症状、体征和影像学改变。 应对措施：若患者确诊间质性肺疾病，应立即停止ADC用药，考虑给予糖皮质激素治疗，并给予呼吸支持等干预性措施，以免危及生命。 （7）心脏毒性 心脏毒性通常表现为QT间期延长、左心室射血分数（LVEF）下降等。 应对措施：应在用药前充分纠正基础心血管疾病，做好基线管理；治疗期间应动态定期复查心电图和心脏超声，必要时完善心肌标志物如脑钠肽或氨基末端脑钠尿肽、心肌肌钙蛋白I或超敏肌钙蛋白的检测。如LVEF降低不可恢复或严重降低，或发生有症状的充血性心力衰竭，应永久停药，必要时请心血管专科会诊。 总之，ADC作为抗肿瘤药物的新星，给患者带来生存获益的同时，也要关注“月之暗面”。各个ADC具有不同的安全性特征，分别有需要特别关注的不良反应。临床医生在用药期间，要对可能产生严重后果的不良反应进行积极预防或给予支持治疗。知之而“治”之，是智也。让我们用好这颗“新型子弹”，一起消灭肿瘤。 审批编号：CN-20241104-00006 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

MANCHESTER, England & MOUNTAIN VIEW, Calif.--( BUSINESS WIRE )--Axalbion, a clinical-stage biopharmaceutical company focused on developing novel medicines to treat cough, announced that the first patient has been dosed in the second part of a Phase 2 proof-of-concept, randomized, placebo-controlled clinical study in chronic cough with AX-8, its lead compound. AX-8 is a potent and selective oral agonist of the transient receptor potential melastatin 8 (TRPM8) ion channel. The company has raised additional financing from existing and new investors to support the trial execution and Phase 3 planning. “We are pleased to announce that Axalbion has launched the second part of its Phase 2 clinical trial with AX-8 in chronic cough, a disease with significant unmet needs,” said Michael Kitt, MD, chief executive officer of Axalbion. “In the first part of this study, AX-8 showed promising results with a robust and sustained reduction in cough frequency, particularly in patients experiencing the greatest throat discomfort, a distressing symptom observed in most chronic cough patients.” Data were presented in an oral session at the American Thoracic Society (ATS) 2023 International Conference. Based on the initial positive findings, the company initiated Part 2 of the study of AX-8 in patients with chronic cough with moderate-to-severe throat discomfort (i.e., those with a throat discomfort visual analog scale score ≥50mm out of 100mm), who are the most likely to benefit from treatment with AX-8. The Phase 2 trial is a randomized, double-blind, placebo-controlled, crossover study evaluating the efficacy and safety of AX-8 in approximately 50 patients with refractory or unexplained chronic cough (RCC/UCC). Patients will receive 40 mg of the drug or matching placebo thrice daily (as opposed to twice daily in Part 1) approximately four hours apart for two weeks, followed by a seven-day washout period, before crossing over to the opposite treatment for two weeks. AX-8 is formulated as an orally disintegrating tablet placed on the tongue. Cough frequency will be assessed with an objective cough recording device. The primary efficacy endpoint will be the placebo-adjusted change in cough frequency compared to baseline. The study will take place at multiple centers in the U.K. and is expected to be completed by the second half of 2025. For more information, please visit clinicaltrials.gov: NCT04866563 . About TRPM8 and AX-8 TRPM8 is expressed in many of the sensory fibers innervating the upper airways. Axalbion believes that activating TRPM8-expressing fibers with AX-8, a potent TRPM8 agonist, will normalize the upper airway sensitivity in chronic cough patients, decreasing coughing and irritation of the throat. David Julius and Ardem Patapoutian were awarded the 2021 Nobel Prize in Physiology or Medicine for their discoveries of thermal and mechanical transducers, including the discovery of TRPM8. Since its cloning in 2002, extensive research has identified TRPM8 as a potential target to relieve symptoms or cure several diseases. Animal models have shown that activation of TRPM8-expressing fibers in the skin inhibits sensory hypersensitivity in peripheral neuropathy and inflammation, as well as itching. About Chronic Cough Chronic cough is defined as a cough lasting for more than eight weeks, often occurring in bouts. More than 80% of patients in tertiary cough clinics have throat irritation which triggers cough bouts, defining a population with oropharyngeal hypersensitivity potentially responding to a topical locally acting drug such as AX-8. After potential triggers such as gastro-intestinal reflux disease (GERD) and asthma have been excluded or treated, cough still remains a significant and common problem for many patients. Chronic cough has a substantial impact on quality of life, for example, around half of female patients having urinary stress incontinence. There are no approved drugs for the treatment of chronic cough in the U.S., making it a significant unmet need affecting approximately 26 million people in the U.S. alone, with approximately three million having RCC/UCC lasting for more than a year and approximately six million having RCC/UCC lasting more than eight weeks and less than one year. About Axalbion Axalbion is a privately held, clinical-stage biotechnology company developing novel medicines for the treatment of chronic cough. The company, founded in December 2016, is based in Manchester, United Kingdom, a region known for its centers of excellence in respiratory research. For further information, please visit www.axalbion.com .

U.S. FDA has granted Orphan Drug Designation to SPG601 for the Treatment of Fragile X Syndrome SPG601 is a novel small molecule that works by correcting specific synaptic dysfunctions in the brain to address core symptoms of Fragile X Syndrome LOS ANGELES, July 23, 2024 (GLOBE NEWSWIRE) -- Spinogenix, Inc., a clinical-stage biopharmaceutical company pioneering first-in-class therapeutics that restore synapses to improve the lives of patients worldwide, today announced that enrollment is now open for their Phase 2 clinical trial evaluating SPG601 for the treatment of adult men with Fragile X Syndrome (FXS), the leading inherited form of intellectual disability and a known cause of autism. The U.S. Food and Drug Administration (FDA) recently cleared the Investigational New Drug (IND) application and granted Orphan Drug Designation for SPG601 for the treatment of people with FXS. "Fragile X patients and their families compose an incredible, yet still underserved community. That is why, during this year’s National Fragile X Awareness Month, we are especially excited to announce that we have begun recruiting for our Phase 2 trial evaluating SPG601 for the treatment of individuals with this difficult condition. This aligns with our commitment to advancing research and treatment options to help people with this condition live better-quality lives, as there are currently no FDA-approved drugs available for those with FXS," said Craig Erickson, M.D., Spinogenix Chief Medical Advisor. “Notably, SPG601 is a novel once-a-day pill that works by binding to BK channels and increasing their activation to correct specific synaptic dysfunctions, a therapeutic approach that we believe can bring much needed hope to individuals and families struggling with FXS.” Stella Sarraf, Ph.D., Spinogenix Chief Executive Officer and Founder, added, "People with FXS and their families face immense challenges every day. This milestone marks a significant step forward in our mission to bring new hope to the people and families affected by this condition. At Spinogenix, we are passionately working to develop first-in-class therapeutics that restore synapses to improve the lives of people worldwide and we are accomplishing this through our trials evaluating SPG601 in FXS and SPG302 in ALS and Alzheimer’s disease. We look forward to exploring the potential of our small molecule platform to address a range of diseases involving synapse loss and dysfunction." This study is a Phase 2 randomized, double blind, placebo-controlled, cross over, single dose of SPG601 and matching placebo in patients with Fragile X syndrome. Enrollment is currently open at the Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, United States. Additional information on the Phase 2 trial is available on ClinicalTrials.gov (NCT06413537). FXS results from the silencing of the Fmr1 gene which leads to changes in mRNA and protein expression that results in abnormalities in synaptic function. Some of these abnormalities have been shown to be a result of a reduction in the amount and activity of large-conductance, calcium-activated potassium (“BK”) channels. Many core symptoms of FXS have been linked to deficient activity of BK channels. In addition to FXS, BK channel expression and activity have been linked to a range of other conditions including neurodegenerative, vascular, and sensory disorders. SPG601 is a novel small molecule BK channel activator that works by binding to BK channels and increasing their activation to correct specific synaptic dysfunctions that underlie these conditions. About Fragile X SyndromeFragile X Syndrome (FXS) is the leading inherited form of intellectual disability and a known cause of autism that results from the silencing of the Fmr1 gene. FXS is an orphan disease affecting approximately 1 in 4-5000 men and 1 in 6-8000 women globally. In addition to intellectual disability, FXS patients endure a wide range of disabling symptoms, including severe anxiety, social aversion, hyperactivity and attention deficit, sensory hypersensitivity, aggression, developmental seizures, and others. Providing care for individuals with FXS often becomes a full-time commitment for at least one parent and imposes significant financial strain, with direct family healthcare costs totaling $4.1 billion annually in the United States alone. Despite the considerable impact of FXS, there are currently no FDA-approved drugs available for those with the condition. About Spinogenix Spinogenix is dedicated to developing transformative therapeutics for conditions involving the loss or dysfunction of synapses. Our lead clinical-stage synaptic regenerative candidate is a first-in-class therapeutic designed to reverse synapse loss and improve cognitive and motor functions in neurodegenerative and neuropsychiatric diseases such as ALS, Alzheimer’s disease, and schizophrenia. In parallel, we are also developing a synaptic function therapeutic designed to improve behavior in Fragile X Syndrome. More information on Spinogenix can be found at www.spinogenix.com or follow us on LinkedIn. Spinogenix Contact info@spinogenix.com Media Contact Kristin Politi, Ph.D.LifeSci Communicationskpoliti@lifescicomms.com(646) 876-4783