奥沙利铂所致神经毒性及其防治研究进展

奥沙利铂是治疗大肠癌的基石药物,可用于大肠癌患者的新辅助化疗、辅助化疗、姑息治疗,也可用于胃癌、卵巢癌的治疗。神经毒性是奥沙利铂治疗过程中比较常见的不良反应,包括运动神经、感觉神经均可受损。神经毒性的发生机制尚不明确,因此对于该种不良反应的有效的预防治疗方法尚在探索中。有学者在研究中发现乙酰胆碱通道,钠离子通道以及瞬时受体电位通道在奥沙利铂神经毒性中具有重要介导作用,基因多样性也会导致患者出现奥沙利铂神经毒性。在探索奥沙利铂神经毒性防治药物时也开始应用黄芪根提取物,单唾液酸神经节苷酯,以上药物在神经毒性防治当中具有显著作用。本文主要是对奥沙利铂所致神经毒性及其防治研究进展展开综述。     

谷胱甘肽预防奥沙利铂所致神经毒性的临床效果观察

目的研究谷胱甘肽预防奥沙利铂所致神经毒性的临床效果。方法 80例采用奥沙利铂进行肿瘤化疗的患者,按照随机分组的原则将其分为研究组和对照组,每组40例,其中对照组患者单纯应用传统疗法,不应用谷胱甘肽;研究组患者化疗前后应用谷胱甘肽,比较两组患者的治疗效果。结果对照组奥沙利铂所致神经毒性的发生率为52.5%,研究组患者奥沙利铂所致神经毒性的发生率为10.0%,两组差异有统计学意义（P〈0.05）。结论谷胱甘肽预防奥沙利铂所致神经毒性的效果良好,应在临床加以推广应用。     

奥沙利铂化疗所致神经毒性反应的预防护理

奥沙利铂（L-OHP）是第三代铂类抗肿瘤药，与氟尿嘧啶（5-FU）联合应用具有协同作用，临床上常应用于消化道肿瘤的治疗。但由于奥沙利铂易引起神经毒性反应，国内临床报道其神经毒性反应可高达90．5％。因此做好奥沙利铂神经毒性反应的预防护理显得尤为重要，现将护理方法报告如下。     

左卡尼汀对预防奥沙利铂周围神经毒性作用的临床观察

目的观察左卡尼汀对奥沙利铂引起的周围神经毒性反应的预防性治疗作用。方法 70例接受奥沙利铂化疗的肿瘤患者随机分为两组,预防性治疗组患者在应用奥沙利铂化疗同时给予左卡尼汀治疗,对照组化疗方案与前组相同但未接受左卡尼汀预防性治疗。分别比较两组患者的神经毒性总发生率、外周感觉神经毒性级别、出现外周神经毒性时间及肿瘤相关性疲劳分级和体力状况评分。结果预防性治疗组神经毒性发生率、外周感觉神经毒性级别均低于对照组,且差异有统计学意义(P<0.05)。结论应用奥沙利铂联合化疗中预防性给予左卡尼汀,可减少化疗相关的神经毒性,值得进一步研究。     

奥沙利铂神经毒性机制及防治研究进展

奥沙利铂是第3代铂类抗癌药物,抗癌谱广、毒副反应轻微是其主要特点。但该药的外周神经毒性发生率却高达90%,是其剂量限制性毒性。现对奥沙利铂(乐沙定)神经毒性表现、分级、发生机制及防治策略进行综述,以便为奥沙利铂疗程持续和达到更好疗效、更小毒性提供依据。     

加味当归四逆汤预防治疗奥沙利铂所致神经毒性35例临床观察

目的:观察加味当归四逆汤预防治疗奥沙利铂所致神经毒性的临床疗效。方法:将70例使用含奥沙利铂方案化疗的患者随机分成治疗组,对照组,治疗组35例采用加味当归四逆汤+化疗,对照组35例采用卡马西平+化疗,比较两组间外周神经毒性的发生率。结果:治疗组和对照组的神经毒性发生率分别为34.3%和54.3%,两组间差异有统计学意义(P<0.05)。结论:加味当归四逆汤预防治疗奥沙利铂所致的外周神经毒性反应,安全有效。     

奥沙利铂化疗致神经毒性反应的护理分析

目的探讨分析奥沙利铂化疗致患者神经毒性反应的护理方法。方法择取2012年6月~2013年6月期间行奥沙利铂化疗患者62例作为观察对象,分析总结因奥沙利铂化疗导致神经毒性反应的患者的护理方法。结果神经毒性反应共50例,其中1度31例,2度12例,3度5例,4度2例,其余12例无明显不良反应发生;本组患者有2例中途停止化疗,其余60例患者均完成化疗。结论对奥沙利铂化疗中出现神经毒性反应的患者进行对症护理的效果良好,可有效帮助患者完成治疗。     

静脉滴注奥沙利铂致急性神经毒性2例

奥沙利铂是第三代铂类抗癌药物,与其他铂类化疗药物相比,在胃肠道肿瘤上体现的特异性抗肿瘤活性更明显。其中神经毒性反应是常见的不良反应,它具有独特的临床表现,其发生机制至今尚不完全清楚,且缺乏标准有效的防治方法。本文通过对2例奥沙利铂所致急性神经毒性病例进行分析,探究出现神经毒性的因素以及减少神经毒性发生的防治方法。     

中医药防治奥沙利铂所致神经毒性进展

奥沙利铂是第三代铂类广谱抗癌药,其疗效更好,毒性更低,已成为大肠癌辅助化疗的一线化疗药。近年来有关中医药防治奥沙利铂神经毒性的临床研究作一综述,供参考。     

钙镁合剂联合谷胱甘肽和卡马西平预防奥沙利铂神经毒性疗效观察

目的:观察钙镁合剂联合谷胱甘肽和卡马西平预防奥沙利铂神经毒性的疗效。方法:65例接受奥沙利铂、5-氟尿嘧啶、亚叶酸钙治疗的胃肠道肿瘤患者,治疗组接受钙镁合剂联合谷胱甘肽和卡马西平治疗,对照组未接受相应预防治疗。结果:3周期后,治疗组出现临床神经毒性的有7例,而对照组有17例,有统计学差异(P=0.036);12周期后,治疗组中出现2～3度神经毒性有2例,而对照组有9例,有统计学差异(P=0.022)。结论:钙镁合剂联合谷胱甘肽和卡马西平能预防奥沙利铂神经毒性。     

奥沙利铂化疗致外周神经毒性的护理体会

奥沙利铂是一种新的铂类抗癌药,具有广谱的体外细胞毒性及体内抗肿瘤活性作用,对顺铂耐药的肿瘤模型仍然有效,常用于转移性结、直肠癌或辅助治疗原发性肿瘤完全切除后三期结肠癌,也适用于经5-氟尿嘧啶治疗失败的结、直肠癌转移患者。但其突出的不良反应是外周感觉神经毒性,主要表现为感觉迟钝和(或)感觉异常,遇冷加重,这种毒性作用与其剂量有关,可表现为急性神经毒性和迟发型感觉神经障碍,影响其疗效和患者的生活质量。研究表明,治疗前后给予肿瘤患者正确有效的护理措施对于提高化疗的疗效和改善患者的预后具有十分重要的临床意义。因此,本文对健康指导、预防、对症护理及心理护理四个方面的护理体会进行了归纳,以期为奥沙利铂毒副反应的有效护理提供更多的参考依据。     

三阴性乳腺癌新型靶向治疗药物研究进展

三阴性乳腺癌（TNBC）即雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体-2（HER-2）表达均为阴性的乳腺癌,是一种异质性疾病,通常具有较高的组织学级别,较激素受体阳性乳腺癌更具侵袭性,且易发生内脏转移。目前,临床对TNBC多采用细胞毒性药物进行常规化疗,但极易产生骨髓抑制、神经毒性等不良反应,导致患者不耐受。使用铂类药物治疗转移性TNBC,药效持续时间短、毒性大,中位总生存期仅9～12个月。鉴于TNBC的化疗效果欠佳,临床迫切需要寻找新的靶向治疗药物,从而根据患者的肿瘤分子亚型制定有效的治疗方案。本文主要就TNBC新型靶向治疗药物的研究进展作一综述。     

Preventing oxaliplatin-induced neurotoxicity: rationale and design of phase Ib randomized,double-blind,placebo-controlled,cross-over trials for early clinical evaluation of investigational therapeutics

Introduction: Oxaliplatin-based chemotherapy has become the standard treatment for colorectal cancer and other gastrointestinal tumor types. Oxaliplatin-induced neurotoxicity is a major treatment-limiting side effect that compromizes the delivery of cancer treatment and causes long-standing neurological deficits that negatively impact upon patient quality of life

Areas covered: The prevention of oxaliplatin-induced neurotoxicity represents an important opportunity for new therapeutic product development to address this major unmet medical need. In this article, we describe a phase Ib clinical trial design, and study procedures and protocols, that we have developed and now propose for the early clinical evaluation of investigational therapeutics for preventing oxaliplatin-induced neurotoxicity.

Expert opinion: Recently, several advances have been made in the development of research methodologies applicable to the clinical evaluation of investigational drugs for preventing oxaliplatin-induced neurotoxicity. As we gain better understanding of the mechanisms of oxaliplatin-induced neurotoxicity, we will be able to use these methods to develop and test more effective and targeted neuroprotective agents that may not only improve patients’ quality of life but also improve treatment delivery and survival outcomes.     

Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review

Peripheral neurotoxicity is a major complication associated with the use of chemotherapeutic agents such as platinum compounds, taxanes and vinca alkaloids. The neurotoxicity of chemotherapy depends not only on the anticancer agent(s) used, the cumulative dose and the delivery method, but also on the capacity of the nerve to cope with the nerve-damaging process. The sensory and motor symptoms and signs of neurotoxicity are disabling, and have a significant impact on the quality of life of cancer patients. Moreover, the risk of cumulative toxicity may limit the use of highly effective chemotherapeutic agents. Therefore, prophylaxis and treatment of peripheral neurotoxicity secondary to chemotherapy are major clinical issues. Acetyl-L-carnitine (ALC), the acetyl ester of L-carnitine, plays an essential role in intermediary metabolism. Some of the properties exhibited by ALC include neuroprotective and neurotrophic actions, antioxidant activity, positive actions on mitochondrial metabolism, and stabilisation of intracellular membranes. ALC has demonstrated efficacy and high tolerability in the treatment of neuropathies of various aetiologies, including chemotherapy-induced peripheral neuropathy (CIPN). In several experimental settings, the prophylactic administration of ALC prevented the occurrence of peripheral neurotoxicity commonly induced by chemotherapeutic agents. In animal models of CIPN, ALC administration promoted the recovery of nerve conduction velocity, restored the mechanical nociceptive threshold, and induced analgesia by up-regulating the expression of type-2 metabotropic glutamate receptors in dorsal root ganglia. These results, plus the favourable safety profile of ALC in neuropathies of other aetiologies, have led to the effects of ALC on CIPN being investigated in cancer patients. Preliminary results have confirmed the reasonably good tolerability profile and the efficacy of ALC on CIPN. The present studies support the use of ALC in cancer patients with persisting neurotoxicity induced by paclitaxel or cisplatin treatment.     

针灸治疗癌性疼痛的临床研究进展

癌痛是中晚期癌症患者常见的临床症状之一,对患者的生存质量产生十分严重的影响,也是临床上很多学者一直致力研究的问题。镇痛剂是临床上用于癌痛最主要的治疗方式,但是由于其本身具有一定的成瘾性及毒副作用,在一定程度上限制了其应用。针灸疗法具有安全、有效、药物不良反应小等特点,在癌痛的治疗中越来越受重视。本研究就近几年来针灸治疗癌痛进行概述,为临床上癌痛的针灸治疗提供参考,同时也为今后的研究方向进行一些必要的探索。     

New oral chemotherapeutic agents for lung cancer

Anticancer treatment has recently shifted to include a broad range of antineoplastic therapies. Old agents are continuously being re-evaluated, and new mechanisms of treatment are rapidly being explored and developed. At the same time, the patient's perceived quality of life, adverse effects of therapy, time demands, and healthcare costs have become paramount in the treatment process. Lung cancer is the most common cause of cancer death in the USA, and because many of the patients are older or debilitated, these issues become all the more important. The oral administration of anticancer therapy offers both quality-of-life and healthcare cost advantages. Oral forms of 3 new cytotoxic agents and 2 novel oral therapies are discussed. Vinorelbine, a vinca alkaloid, has well documented activity in non-small cell lung cancer. Myelosuppression is dose limiting; neurotoxicity is rare. Satraplatin (JM-216), an oral platinum derivative, shows activity in lung cancer with a favourable adverse effect profile, with no neurotoxicity or nephrotoxicity. The oral topoisomerase I inhibitor topotecan may be ideal for obtaining long term low plasma drug concentrations, which appears to maximise efficacy. LGD-1069 is a retinoid X receptor agonist that modulates cell proliferation, and BAY-129566, a matrix metalloproteinase inhibitor, appears to interrupt both the processes of angiogenesis and metastasis. LGD-1069 and BAY-129566 are nontraditional anticancer agents which may be used in conjunction with chemotherapy, other modalities, or in prevention. These 5 agents will be discussed with particular reference to recent developments in the treatment of lung cancer.     

表皮生长因子受体酪氨酸激酶抑制剂在肺癌以外的应用进展

表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKIs)主要用于晚期非小细胞肺癌的分子靶向治疗,随着EGFR-TKIs的越来越深入研究,发现EGFR及其配体参与了包括乳腺癌、胰腺癌等在内的不同人类癌症发病过程。因此,EGFR-TKIs的治疗对象也不再局限于晚期非小细胞肺癌,其对乳腺癌、胰腺癌、头颈癌、食管癌和宫颈癌等恶性肿瘤也有较好的抑制作用,并且与EGFR-TKIs联合用药往往比单独用药效果更好。该文讨论了EGFR-TKIs在治疗肺癌以外其他癌症的应用研究,以及EGFR-TKIs与其他药物联合治疗乳腺癌、胰腺癌等恶性肿瘤的潜在应用前景。     

Dextromethorphan: a review of N-methyl-d-aspartate receptor antagonist in the management of pain

Dextromethorphan (DM) is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, which is widely used as an antitussive agent. DM also prevents neuronal damage and modulates pain sensation via noncompetitive antagonism of excitatory amino acids (EAAs). DM has been found to be useful in the treatment of pain in cancer patients and in the treatment of methotrexate-induced neurotoxicity. Clinical studies with DM in cancer patients are reviewed in this article.     

雄黄抗癌作用的研究进展

中药雄黄在我国传统医学中应用历史悠久,近年来在肿瘤的治疗中发挥着越来越大的作用,本文介绍雄黄抗癌作用的研究与进展,包括治疗研究、作用机理、不良反应及其新剂型—纳米雄黄的研发等,并对雄黄抗癌作用的未来进行展望。     

Delayed oxaliplatin-associated neurotoxicity following adjuvant chemotherapy for stage III colon cancer

Oxaliplatin-containing chemotherapy regimens are utilized commonly for metastatic colorectal cancer and increasingly in the adjuvant setting following surgical resection. The dose-limiting toxicity is neurotoxicity. Acute neurotoxicity is cold induced and transient. Chronic neurotoxicity usually has a predictable clinical course. It is manifested by paresthesias and dysesthesias of gradually prolonged duration that occur between treatment cycles, and increase in intensity and duration with the cumulative dose. We report here a case of a patient who developed significant grade 3 chronic neuropathy following completion of 6 months of adjuvant oxaliplatin-containing chemotherapy for stage III colon cancer. The neurotoxicity was not preceded by any transient symptoms characteristic of chronic oxaliplatin neuropathy and its onset was unpredictable. Delayed neurotoxicity is a complication which must be considered for patients receiving adjuvant therapy and attempts to utilize the minimum effective cumulative dose of oxaliplatin are warranted.