Type 2 diabetes mellitus and prognosis in early stage breast cancer women

It has been suggested that type 2 diabetes mellitus may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The aim of this study was to determine the impact of diabetes on disease-free survival (DFS) following mastectomy for breast cancer patients. The cases included in this retrospective study were selected from breast cancer women who had undergone mastectomy and completed adjuvant chemotherapy from 1998 to 2010. Patients were classified into two groups: diabetic and non-diabetic. Patients' age, sex, menopausal status, body mass index (BMI), histopathological features, tumor size, lymph node involvement, hormone receptor and HER2-neu status, and treatment types were recorded. There were 483 breast cancer patients included in the study. Postmenopausal patients' rate (53.7% vs. 36.8%, P = 0.016) and mean BMI levels were statistically higher (32.2 vs. 27.9, P = 0.007) in diabetic patients. There was no statistical difference for histological subgroup, grade, ER and PR positivity, HER2-neu overexpression rate, and tumor size between the diabetic and non-diabetic group. Lymph node involvements were statistically higher in diabetic patients compared with non-diabetic patients (P = 0.013). Median disease-free survival is 81 months (95% CI, 61.6-100.4) in non-diabetic patients and 36 months (95% CI, 13.6-58.4) in diabetic patients (P < 0.001). The odds ratio of recurrence was significantly increased in those with HER2-neu overexpression and lymph node involvement and decreased with PR-positive tumors. Our results suggest that diabetes is an independent prognostic factor for breast cancer.     

New pharmacological effect of fulvestrant to prevent oxaliplatin-induced neurodegeneration and mechanical allodynia in rats

Oxaliplatin, which is widely used as chemotherapy for certain solid cancers, frequently causes peripheral neuropathy. Commonly described neuropathic symptoms include aberrant sensations such as mechanical allodynia (hypersensitivity to normally innocuous stimuli). Although oxaliplatin neuropathy is a dose-limiting toxicity, there are no established preventive strategies available at present. By screening several sets of small-molecule chemical libraries (more than 3,000 compounds in total) using a newly established in vitro high-throughput phenotypic assay, we identified fulvestrant, a clinically approved drug for the treatment of breast cancer in postmenopausal women, as having a protective effect on oxaliplatin-induced neuronal damage. Furthermore, histological and behavioural analyses using a rat model of oxaliplatin neuropathy demonstrated the in vivo efficacy of fulvestrant to prevent oxaliplatin-induced axonal degeneration of the sciatic nerve and mechanical allodynia. Furthermore, fulvestrant did not interfere with oxaliplatin-induced cytotoxicity against cancer cells. Thus, our findings reveal a previously unrecognised pharmacological effect of fulvestrant to prevent oxaliplatin-induced painful peripheral neuropathy without impairing its cytotoxicity against cancer cells and may represent a novel prophylactic option for patients receiving oxaliplatin chemotherapy.     

Neurological complications of medical anti-cancer therapies

This review describes the features of central and peripheral neurological disorders caused by anti-cancer chemotherapy and supportive medications, such as antiepileptic drugs, glucocorticosteroids and opioids, frequently used in cancer patients. Diffuse encephalopathy with or without epileptic seizures, cerebellar disorders and aseptic meningitis may occur after systemic administration of conventional drug doses, but their incidence is much higher when either high-dose chemotherapy, or intrathecal or intracarotid administration is used. Spinal cord and/or spinal root lesions have been reported after intrathecal administration of methotrexate or cytosinearabinoside. Anti-cancer chemotherapy is the leading cause of peripheral neuropathy in cancer patients. The main culprits are vinca alkaloids, platinum derivatives and taxanes. Anti-cancer chemotherapy has no significant toxic effect on muscle tissue, but heavy administration of glucocorticosteroids is a common cause of disabling, predominantly pelvic, muscle atrophy.     

激素受体阳性乳腺癌脑转移药物治疗研究进展

目的 乳腺癌是仅次于肺癌最易发生脑转移的原发肿瘤.激素受体阳性乳腺癌是转移性乳腺癌的主体,脑转移是该类患者的主要死亡原因,但目前对于激素受体阳性乳腺癌脑转移(breast cancer brain metastases,BCBM)的有效治疗报道较少.本研究旨探讨激素受体阳性BCBM药物治疗的相关研究进展.方法 应用PubMed及CNKI期刊全文数据库检索系统,以"乳腺癌、脑转移和激素受体阳性乳腺癌"等为,检索2005-01-2016-06相关文献,共检测到中文文献128条,英文文献55条.纳入标准:1)BCBM的危险因素及其预后;2)BCBM的当前治疗选择;3)激素受体阳性BCBM药物治疗.根据纳入标准,符合分析的文献25篇.结果限制BCBM药物治疗进展的主要原因是血脑屏障的存在.激素在BCBM治疗中的疗效尚不明确,但有大量个案报道他莫昔芬等内分泌药物对BCBM治疗有效.非对照试验表明某些细胞毒类药物,如卡培他滨、替莫唑胺(temozolomide,TMZ)和卡莫司汀晶片植入剂,对激素受体阳性BCBM有效,但没有足够证据支持具体的治疗方案.免疫抑制剂abemaciclib在激素受体阳性BCBM患者中的应用正处于Ⅱ期临床试验阶段.虽然高分子药物难以通过完整的血脑屏障,但研究证实部分单克隆抗体,如曲妥珠单抗和贝伐单抗,对BCBM治疗有效.纳米药物传递系统能提高中枢神经系统药物转移,有较好发展前景.由纳米颗粒包裹的多柔比星和etirinotecanpegol对治疗激素受体阳性BCBM有一定的疗效.结论尽管目前没有专门批准用于激素受体阳性BCBM系统治疗的药物,但有大量的临床试验正在进行中,将为临床治疗带来启示.     

Neurotoxicity and dermatologic toxicity of cancer chemotherapy

Neurological dysfunction is a common adverse effect of many chemotherapeutic agents. Any part of the peripheral or central nervous system can be affected. Various clinical syndromes including encephalopathy, cerebellar syndrome, cranial neuropathy, seizure,myelopathy, and peripheral neuropathy commonly occur. In several drugs, neurotoxicity is a dose-limiting toxicity. Multiple factors such as cumulative dose, route of administration, drug metabolism and synergistic effects of other drugs or radiotherapy impact the incidence and severity of neurotoxicity. Much of the research in chemotherapy-induced neuropathies has been focused on the goal of ameliorating or preventing the neurotoxicity without altering the effectiveness of the medication. Various dermatologic complications of cancer chemotherapy such as extravasation, hyperpigmentation, nail change, radiation recall reaction and hypersensitivity reaction can occur. In extravasation, many cytotoxic agents are irritants or non-vesicants, however,a significant number of commonly used drugs are classified as vesicants, including the vinca alkaloids anthracyclines and taxanes. Extravasation of vesicant drugs into the subcutaneous tissue results in severe local pain and ulceration with progressive tissue destruction. Strategies to reduce the incidence of extravasation and minimize its associated morbidity are crucial to quality of life for cancer patients. The more common clinical features of chemotherapy-induced neurologic and dermatologic toxicities are discussed below.     

Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group.

PURPOSE: The purpose of this study was to determine whether amifostine (WR-2721) prevents or ameliorates clinically significant (grade 2 to 4) neurotoxicity associated with cisplatin and 3-hour paclitaxel chemotherapy.Materials and METHODS: The chemotherapy program consisted of intravenous paclitaxel 175 mg/m2 over 3 hours followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2 administered over 90 minutes beginning 15 minutes after amifostine administration. At baseline, before each treatment cycle, and for 3 months after completing chemotherapy, patients were evaluated for evidence of neurotoxicity and other treatment-related adverse effects using three methods: standard clinical evaluation (National Cancer Institute common toxicity criteria [CTC] grading), a neurotoxicity questionnaire to assess symptoms and limitations imposed by peripheral neuropathy, and vibration perception threshold (VPT) testing. RESULTS: Four of 27 assessable patients developed grade 2 to 4 neurotoxicity based on clinical assessments and CTC grading. This number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed. CONCLUSION: Amifostine's level of activity in this trial was insufficient to warrant further study in a phase III trial. Based on the receiver operating characteristic analysis, it would appear that VPT measurements are less sensitive to the development of peripheral neuropathy than the neurotoxicity questionnaire. The questionnaire, referred to as the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, may be used instead of VPT measurements in future studies of chemotherapy-induced peripheral neuropathy.     

Treatment strategies for chemotherapy-induced peripheral neuropathy: potential role of exercise

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting effect of cancer therapy that often has negative implications on a patient’s quality of life. The pain associated with CIPN has long been recognized as one of the most difficult types of pain to treat. Historically, much effort has been made to explore pharmacological therapies aimed at reducing symptoms of CIPN. While many of these agents provide a modest relief in the symptoms of peripheral neuropathy, many have been shown to have additional negative side effects for cancer patients. Therefore, the authors suggest exercise rehabilitation as one lifestyle modification that may positively impact the lives of patients with CIPN. To our knowledge, there are currently no published clinical trials examining the role of exercise in preserving neurological function following chemotherapy. However, investigations using low-to-moderate intensity exercise as an intervention in patients with diabetic peripheral neuropathy and hereditary motor and sensory neuropathies have produced promising results. Given that cancer patients appear to tolerate exercise, it seems plausible that exercise rehabilitation could be used as an effective strategy to minimize CIPN-induced detriments to quality of life.     

Chemotherapy-induced peripheral neuropathy and rehabilitation: A review

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication after chemotherapy that can damage the sensory, motor, autonomic, or cranial nerves in approximately 30%–60% of patients with cancer. CIPN can lead to detrimental dose modifications and/or premature chemotherapy discontinuation due to patient intolerance. The long-term impact of CIPN is particularly challenging and can have a profound impact on the quality of life (QoL) and survivorship. However, this condition is often underdiagnosed. No agents have been established to prevent CIPN. Pre-chemotherapy testing is recommended for high-risk patients. Duloxetine is considered a first-line treatment, whereas gabapentin, pregabalin, tricyclic antidepressants, and topical compounding creams may be used for neuropathic pain control. Home-based, low-to-moderate walking, and resistance exercise during chemotherapy can reduce the severity and prevalence of CIPN symptoms, especially in older patients. Pre-habilitation and rehabilitation should be recommended for all patients receiving cytotoxic chemotherapies. The purpose of this article is to review common chemotherapeutic drugs causing CIPN, risk factors, diagnosis and treatment of CIPN, and evidence of the benefits of rehabilitation.     

Beyond symptomatic relief for chemotherapy‐induced peripheral neuropathy: Targeting the source

Chemotherapy‐induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy‐induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism‐based, disease‐modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod‐shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy “currency” adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro‐oxidative stress represent crucial final common pathways of CIPN. Herein, the authors discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro‐oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin‐μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti‐inflammatory mediators including interleukin 10. This review hopefully will contribute toward bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289‐98 . © 2018 American Cancer Society.     

Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain are challenging complications of cancer treatment. Many of the major classes of chemotherapeutics can cause neurotoxicity and significantly modulate the immune system. There is ongoing investigation regarding whether reciprocal crosstalk between the nervous and immune systems occurs and, indeed, contributes to neuropathic pain during treatment with chemotherapeutics. An emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN. Here, we discuss recent findings, which provide insight into this complex process of neuroimmune interactions. Findings show limited infiltration of leukocytes into the nervous system of CIPN animals and varying degrees of peripheral and central glial activation depending on the chemotherapeutic drug, dose, schedule, and timing. Most evidence suggests an increase in pro-inflammatory cytokine expression and changes in immune signalling pathways. There is, however, limited evidence available from human studies and it remains unclear whether neuroinflammatory responses are the cause of neuropathy or a bystander effect of the chemotherapy treatment.     

Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer.

BACKGROUND: Because of the increasing number of long-term survivors of metastatic testicular germ-cell cancer, a general concern has been secondary morbidities, especially cardiovascular risk factors. PATIENTS AND METHODS: Thirty-two patients treated with cisplatin- and doxorubicin-containing chemotherapy > or = 13 years before the time of analyses were evaluated for neuro-, oto-, pulmonary-, vascular- and gonadal toxicity including evaluation of myocardial damage and cardiovascular risk factors and analysis of microcirculation. RESULTS: Thirty percent of the patients showed abnormal left ventricle function. Elevated follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in 75% of patients were often associated with low testosterone levels. Elevated total cholesterol levels were found in 82% and higher triglyceride levels in 44% of patients, most of them were overweight. About 25% of the patients developed diastolic arterial hypertension after chemotherapy. Reduced hearing was confirmed in 23% of patients, especially at frequencies higher than 3000 Hz. Moreover, 53% of patients presented transient evoked otoacoustic emissions. In 38% of patients non-symptomatic neuropathy was detected, in 28% symptomatic neuropathy, and in 6% disabling polyneuropathy. In 80% of patients with neuropathic symptoms additional morphological and functional abnormalities were found by nailfold capillary videomicroscopy, compared to only 57% of the patients without neuropathic symptoms. CONCLUSIONS: Patients cured by cisplatin-based chemotherapy for metastatic testicular cancer have to be cognizant of their unfavorable cardiovascular risk profile, that might be a greater risk than developing a relapse or second malignancy.     

Meet the expert: How I treat chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, often irreversible and disabling adverse effect of many commonly used chemotherapeutic agents. Older patients are at particular risk of developing CIPN due to comorbid conditions affecting the health of peripheral nerves. Symptoms of CIPN include paresthesias, dysesthesias, sensory loss, motor weakness, dysautonomia, and falls. Pharmacologic management of CIPN involves use of medications including antidepressants, anticonvulsants, and topical treatments for modulation of neuropathic pain. These medications should be used and monitored carefully in older patients as they may increase the risk of confusion, falls, and drug-drug interactions. Patients with CIPN are at an increased risk of falls and should be considered for supportive care interventions including physical and occupational therapy, assistive devices, and safety evaluations. Surveillance of CIPN during and following treatment is essential. The development of neuropathic symptoms may require dose reduction, drug holiday, or transitioning to another chemotherapeutic agent. Symptoms of CIPN typically improve following exposure to neurotoxic therapy, although in older adults the rate of improvement may be slow, and recovery is often incomplete. Early involvement of a neurologist should be considered in patients with atypical, progressive, motor- or autonomic- predominant presentations of neuropathy. Patients with refractory neuropathic pain or those who cannot tolerate standard symptomatic treatment should be referred to a pain specialist or palliative care.     

Association between diabetes mellitus and adverse characteristics of breast cancer at presentation

Type 2 diabetes mellitus is associated with increased incidence and inferior outcome of various malignancies. The aim of this study was to explore the impact of type 2 diabetes on breast cancer characteristics at presentation. The study population included 79 diabetic and 158 age-matched non-diabetic patients. Parity, country of birth, co-morbidity other than diabetes, and mode of diagnosis were similar in both groups. Mean body mass index (BMI) was higher among diabetic patients. Tumour stage and size were higher among diabetic patients and the differences remained significant after adjustment for BMI. Moreover, after adjustment for BMI, breast cancer among diabetic patients was more often hormone receptor negative. Our results show that diabetes mellitus is associated with negative prognostic factors at breast cancer presentation.     

二甲双胍在乳腺癌中抗肿瘤作用研究进展

临床前研究表明降糖药二甲双胍对乳腺癌有抗肿瘤作用,能降低糖尿病患者乳腺癌发病风险和死亡风险,也能提高乳腺癌患者新辅助化疗后病理完全缓解率。体内外实验表明二甲双胍有效抑制各种乳腺癌细胞和移植瘤,并和化疗药物、HER2靶向药物、新型抗肿瘤药物有良好协同作用。主要分子机制包括全身性下调胰岛素及相关信号通路、肿瘤细胞内激活LKBl／AMPK、抑制下游mTOR通路等。目前各国开展了多个临床试验评估--sp双胍在乳腺癌防治中的应用价值。     

Patient guide to peripheral neuropathy.

PURPOSE/OBJECTIVES: To describe a booklet used to educate patients who experience peripheral neuropathy secondary to neurotoxic chemotherapy treatment. DATA SOURCES: Journal articles, neurologic physical assessment, symptom management books. DATA SYNTHESIS: The booklet defines peripheral neuropathy, the types of nerves most often affected, common causes and symptoms, and management strategies with an emphasis on safety issues. It contains a list of referral sources for additional management information and a glossary of terms related to peripheral neuropathy. CONCLUSIONS: The booklet is useful for patients in their daily management of peripheral neuropathy that has occurred as a side effect of neurotoxic chemotherapy treatment. IMPLICATIONS FOR NURSING PRACTICE: Nurses can use this information to educate patients and their caregivers about peripheral neuropathy. The booklet offers strategies to manage this side effect and maintain a safe home environment and workplace. It also offers sources of information and referrals that may benefit patients with peripheral neuropathy.     

Diabetes mellitus impairs the response to intra-arterial chemotherapy in hepatocellular carcinoma

Diabetes mellitus is associated with a poorer outcome in patients with hepatocellular carcinoma. The impact of diabetes mellitus on the treatment of hepatocellular carcinoma, especially chemotherapy, is uncertain. Intra-arterial chemotherapy is one of the therapeutic options of unrespectable hepatocellular carcinoma. To clarify this point, we analyze the therapeutic effect of intra-arterial chemotherapy in unrespectable hepatocellular carcinoma patients with or without diabetes mellitus. Fifty-two patients with advanced hepatocellular carcinoma underwent intra-arterial chemotherapy with cisplatin and fluorouracil. Tumor response was assessed by computed tomography. An in vitro hepatocellular carcinoma cell line, Hep G2, was evaluated for the cytotoxic effect of cisplatin and fluorouracil in different concentrations of insulin and glucose mimicking diabetic conditions. Fifty-two patients were included, 14 had diabetes and 38 were non-diabetics. Non-diabetic patients had a lower rate of progressive disease (16% vs. 43%, P = 0.039). The median time to progression was significantly longer in non-diabetics compared with the diabetic counterpart (a median of 206 days vs. 88 days, P = 0.02). In the hepatocellular carcinoma cell line, Hep G2, insulin rather than glucose was more important for promoting cell proliferation and enhancing the drug resistance of cisplatin or fluorouracil. Our study showed that intra-arterial chemotherapy for unrespectable hepatocellular carcinoma was less effective in diabetic patients than the non-diabetic counterpart in terms of the progression-free rate and time to disease progression survival.     

癌症患儿神经性疼痛治疗进展

癌性神经性疼痛是指由于损害或疾病直接影响躯体感觉系统而产生的疼痛;当然,并不是所有躯体感觉系统受损都会导致神经性疼痛。在儿童癌症患者中,引起神经性疼痛原因有多种,如化疗药（如长春新碱、顺铂和紫杉醇等）、脊髓损伤、肿瘤对组织及神经的直接损伤等。神经性疼痛发生率虽低于躯体性疼痛,但其更难治疗,需要更多的临床随访,更复杂的用药管理,以及频繁的非药物干预。为了更好地控制癌症患儿神经性疼痛,本文拟对癌症患儿神经性疼痛的治疗方法进行综述,以更好地指导临床治疗。     

The influence of diabetes severity on receipt of guideline-concordant treatment for breast cancer

Diabetes severity may influence breast cancer treatment choices. We examined whether receipt of guideline-concordant breast cancer treatment varied with diabetes severity. Cancer registry data from seven states regarding 6,912 stage I–III breast cancers were supplemented by medical record abstraction and physician verification. We used logistic regression models to examine associations of diabetes severity with guideline-concordant locoregional treatment, adjuvant chemotherapy, and hormonal therapy adjusted for sociodemographics, comorbidity, and tumor characteristics. We defined guideline concordance using National Comprehensive Cancer Network guidelines, and diabetes and comorbidities using the Adult Comorbidity Evaluation-27 index. After adjustment, there was significant interaction of diabetes severity with age for locoregional treatment (p = 0.001), with many diabetic women under age 70 less frequently receiving guideline-concordant treatment than non-diabetic women. Among similarly aged women, guideline concordance was lower for women with mild diabetes in their late fifties through mid-sixties, and with moderate/severe diabetes in their late forties to early sixties. Among women in their mid-seventies to early eighties, moderate/severe diabetes was associated with increased guideline concordance. For adjuvant chemotherapy, moderate/severe diabetes was less frequently associated with guideline concordance than no diabetes [OR 0.58 (95 % CI 0.36–0.94)]. Diabetes was not associated with guideline-concordant hormonal treatment (p = 0.929). Some diabetic women were less likely to receive guideline-concordant treatment for stage I–III breast cancer than non-diabetic women. Diabetes severity was associated with lower guideline concordance for locoregional treatment among middle-aged women, and lower guideline concordance for adjuvant chemotherapy. Differences were not explained by comorbidity and may contribute to potentially worse breast cancer outcomes.     

Research on complementary/alternative medicine for patients with breast cancer: a review of the biomedical literature.

PURPOSE: This article reviews English-language articles published in the biomedical literature from 1980 to 1997 that reported results of clinical research on complementary and alternative medical treatments (CAM) of interest to patients with breast cancer. METHODS: We searched 12 electronic databases and the bibliographies of the retrieved papers, review articles, and books on CAM and breast cancer. The retrieved articles were grouped by end point: breast cancer (eg, tumor size, survival), disease-related symptoms, side effects of treatment, and immune function. Within each end point, we organized the articles by modality and assessed study design, findings, and qualitative aspects. RESULTS: Of the more than 1,000 citations retrieved, 51 fit our criteria for review. Of the articles reviewed, 17 were randomized clinical trials; three of these were trials of cancer-directed interventions, two of which involved the same treatment (melatonin). Seven articles described observational studies, and the remainder were reports of phase I or II trials. Relatively few CAM modalities reportedly used by many breast cancer patients were mentioned in articles retrieved by this process. Most articles had shortcomings. CONCLUSION: Although many studies had encouraging results, none showed definitively that a CAM treatment altered disease progression in patients with breast cancer. Several modalities seemed to improve other outcomes (eg, acupuncture for nausea, pressure treatments for lymphedema). If CAM studies are well-founded, well-designed, and meticulously conducted, and their hypotheses, methods, and results are reported clearly and candidly, research in this controversial area should acquire credibility both in the scientific community and among advocates of unconventional medicine.     

奥沙利铂神经毒性机制及预测

 作为大肠癌的主要化疗药物之一,奥沙利铂的应用正逐步扩展到其他肿瘤的治疗中,然而奥沙利铂相关外周神经病变却限制了其临床应用。奥沙利铂神经毒性的机制尚未明确,最新研究认为急性神经毒性是通过改变Na+短暂电导介导的;体外实验证实了丝裂原活化蛋白激酶(MAPK)在奥沙利铂慢性神经病变中的作用。多种指标可用于预测奥沙利铂相关的外周神经病变,为实现个体化药物治疗、提高化疗的连续性带来了希望。