国产大剂量顺铂耳毒性的临床观察

耳毒性是顺铂(cis-platin,DDP)的一个重要毒副反应。近年来随着水化利尿和高渗盐水等措施的应用,DDP用量明显提高,肾毒性虽有所减低但耳毒性却相应加重。大剂量DDP用法不当可导致完全失听,多数报道耳毒性的发生率在50％左右,而国产大剂量DDP治疗后耳毒性的发生率却未见报道。为此,我们进行了DDP治疗后耳毒性的观察。     

草酸铂的特殊毒性

目的探讨抗瘤新药草酸铂的毒性,尤其是临床尚未报道的毒性.方法对用草酸铂为主方案治疗的108例胃肠肿瘤患者的临床资料进行回顾性分析.结果除常见毒性外,尚发现草酸铂致肾衰1例,耳毒性3例.结论对老年,原有耳、肾脏病变者在应用草酸铂过程中仍应注意肾衰及听力损害的可能.     

顺铂肾毒性预防的研究进展

顺铂是临床应用最广泛的抗癌药物，如何减轻其肾毒性是当前的研究热点，并且已取得可喜进展，如调整给药时间，控制水铂，血浆铂峰浓度，改变谷胱甘肽含量，应用高氯液体，止吐剂，微量元素，氨基酸，抗生素，糖皮质激素，含苯甲酸基团药物，硫代氨基甲酸酯类药物，中药等均可不同程度地降低顺铂的肾毒性，对其临床应用具有重要意义。     

奥沙利铂周围神经系统毒性的预防与治疗

周围神经毒性是奥沙利铂的临床剂量限制性毒性,随着对其机制的认识,临床上已有一些预防和治疗其毒性的药物,目前报道有预防和治疗作用的药物有镁盐、钙盐、卡马西平、阿米硫定、谷胱甘肽和加巴喷丁等。现就奥沙利铂神经毒性临床预防和治疗药物的进展做一综述。     

奥沙利铂周围神经系统毒性的预防与治疗

周围神经毒性是奥沙利铂的临床剂量限制性毒性,随着对其机制的认识,临床上已有一些预防和治疗其毒性的药物,目前报道有预防和治疗作用的药物有镁盐、钙盐、卡马西平、阿米硫定、谷胱甘肽和加巴喷丁等。现就奥沙利铂神经毒性临床预防和治疗药物的进展做一综述。     

奥沙利铂的神经毒性及其防治

奥沙利铂是第三代铂类抗肿瘤药物，它的分子结构与顺铂相似．但是它含有一个二氨环己烷基团。这一修饰增强了其对DNA修复的抗性，并使得奥沙利铂-DNA加合物一旦形成后，能够有效地阻止DNA的复制。在临床研究中，奥沙利铂显示出了对各种不同实体肿瘤的广泛抗癌谱，已被广泛应用于结直肠癌、胰腺癌、卵巢癌、乳腺癌和肺癌等的治疗．尤其是在结直肠癌中．奥沙利铂更表现出了顺铂和卡铂所没有的抗癌活性。虽然奥沙利铂作为单药对结直肠癌只有中等强度的治疗效果，但它与氟尿嘧啶类药物（如5-Fu）和亚叶酸类药物[甲酰四氢叶酸（LV）]联合使用，无论在临床前期试验模型中还是在临床试验中都表现出了显著的治疗效果。     

中药预防和减轻顺铂肾毒性的临床和实验研究

化学治疗是恶性肿瘤的主要治疗方法之一。顺铂(PDD)是一种常用的新型抗癌药,临床使用广泛。顺铂对肾脏有一定的毒性,大剂量顺铂对肾脏的毒性更大,它是临床应用受到限制的主要原因。化疗引起的肾功能衰竭,临床上并不少见。我们采用中药复方进行预防和减轻化疗药肾毒性的临床和实验研究,现将研究结果报告如下。     

顺铂肾毒性作用的初步实验研究

顺铂(DDP)的肾毒性作用是影响临床应用的关键因素,其机理目前尚不清楚。本文进行了初步动物试验观察,以提供初步参考材料。     

草酸铂周围神经毒性机制研究进展

草酸铂是少数几种治疗转移性大肠癌有效的化疗药物之一，而周围神经毒性是其剂量限制性毒性。为了进一步提高药物剂量，从而提高肿瘤治疗效果，国内外学者从形态学、药理学、神经电生理学及神经生物学等角度对其周围神经毒性机制进行了较广泛的研究，同时也探索了相应的预防措施。目前大部分预防措施尚处于临床前期及Ⅰ期研究阶段，仍需大规模临床随机试验进一步验证。     

文拉法辛预防奥沙利铂所致神经毒性的临床观察

目的:探讨文拉法辛对奥沙利铂所致神经毒性的预防作用.方法:将103例接受含奥沙利铂方案化疗的恶性肿瘤患者随机分成文拉法辛组(58例)和对照组(45例),文拉法辛组(随机分为A、B两组)化疗同时给予口服文拉法辛,其中A组28例给予文拉法辛37.5 mg,1次/d,B组30例给予文拉法辛75.0 mg,1次/d,对照组化疗同时给予口服安慰剂.按照NCI-CTC 3.0奥沙利铂神经毒性分级标准,观察不同组别急、慢性神经毒性以及不良反应发生的差异.结果:A组急性神经毒性的发生率(57.1％)稍高于B组(56.7％),但A、B两组均明显低于对照组的80.0％,A组与对照组发生率比较差异有统计学意义,P=0.036;B组与对照组发生率差异有统计学意义,P=0.03;而A组与B组发生率差异无统计学意义,P=0.971.化疗3个周期时,A组、B组和对照组Ⅰ～Ⅱ度神经毒性的发生率分别为35.7％、40.0％和42.4％,差异无统计学意义,P＞0.05.化疗6个周期时,A组Ⅰ～Ⅱ度神经毒性发生率为48.0％,低于B组的53.6％,差异无统计学意义,P=0.685;而A组慢性神经毒性发生率低于对照组的76.9％,差异有统计学意义,P=0.017；B组慢性神经毒性发生率低于对照组,差异有统计学意义,P=0.022.化疗9个周期时,A组慢性神经毒性发生率为59.1％低于B组的62.5％,但差异无统计学意义,P=0.813;而A组Ⅰ～Ⅱ度神经毒性发生率低于对照组的87.9％,差异有统计学意义,P=0.027.B组慢性神经毒性发生率低于对照组,差异有统计学意义,P=0.046.A、B两组恶心、呕吐、乏力不良反应的发生率均较对照组明显增多,差异有统计学意义,P＜0.05.结论:文拉法辛能明显减少奥沙利铂所致急慢性神经毒性发生.     

Ototoxicity and cancer therapy

Ototoxicity is a well‐established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health‐related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration‐approved otoprotectants are currently available. Prospective monitoring for ototoxicity allows for comparison of auditory outcomes across clinical trials, as well as for early detection, potential alterations in therapy, and auditory intervention and rehabilitation to ameliorate the adverse consequences of hearing loss. Cancer 2016;122:1647‐58 . © 2016 American Cancer Society.     

Ototoxicity of cisplatin plus standard radiation therapy vs. accelerated radiation therapy in glioblastoma patients

Summary Purpose: To assess the effect of cisplatin (CDDP) plus concurrent radiation therapy on hearing loss. Methods: 451 patients with glioblastoma multiforme (GBM) were randomly assigned after surgery to: Arm A: Carmustine (BCNU) + standard radiation therapy (SRT); Arm B: BCNU + accelerated radiation therapy (ART: 160 cGy twice daily for 15 days); Arm C: CDDP + BCNU + SRT; or Arm D: CDDP + BCNU + ART. Patients on arms C and D received audiograms at baseline, and prior to the start of RT, and prior to cycles 3 and 6. Otologic toxicities were recorded at each visit. Results: 56% of patients had hearing loss at baseline. 13% and 50% of patients experienced worsening ototoxicity after 1 year of treatment in arms A and B vs. C and D, respectively, with 13% of those on arms C and D experiencing significant ototoxicity (≥ grade 3) at 6 months. Increasing age was associated with an increased risk of ototoxicity. Conclusions: Increased exposure to CDDP increases the risk of ototoxicity over time. Older patients are more susceptible to hearing loss with CDDP. The low proportion of patients with clinically significant ototoxicity suggests that baseline screening is unnecessary in GBM patients.     

ATP生物荧光法在中晚期胃癌化疗药物筛选中的应用

[目的]探讨三磷酸腺苷生物荧光肿瘤抗癌药物敏感性分析（ATP-TCA）在胃癌患者化疗方案中的指导价值。[方法]应用ATP-TCA法,体外检测53例胃癌细胞对7种（组）常用抗癌药物的敏感性。[结果]ATP-TCA法对胃癌标本的可评估率为96.23%。胃癌细胞对5-Fu联合铂类药物方案（5-Fu＋DDP、5-Fu＋CBP、5-Fu＋LOHP）与5-Fu、DDP、CBP、LOHP等单药相比敏感度有显著性差异（χ2=11.47,P〈0.01）。应用ATP-TCA结果指导胃癌临床化疗的有效率为66.67%,总预测准确率为74.51%,敏感度为72.34%,特异性为100.00%。[结论]ATP-TCA法是一种有效的肿瘤化疗药物药敏性分析实验,对指导胃癌患者个体化化疗有着重要作用。     

The Effect of Radiation and Cytotoxic Platinum Compounds on the Growth of Normal and Tumour Bladder Explant Cultures

Using an explant tissue culture model developed by this group for use with human surgical and biopsy specimens, data are presented showing the response of normal and tumor bladder urothelium to radiation in combination with cis- and carboplatin. Cellular response is measured after two weeks in culture as a reduction in the extent of outgrowth explant. The outgrowth has been shown to be growing and to be epithelial. Results showed that when either drug or radiation is used singly, the tumour is resistant to treatment while the normal cells are severely affected. However, appropriate combinations of either drug with radiation reverse the unfavourable therapeutic ratio and result in higher tumour cell kill. The model may be useful for investigating mechanisms of radiatiodchemotherapy action at the cellular level and, if integrated into appropriate clinical trials, may serve as an easy-to-use in vitro test for optimising single agent or combination therapy regimens.     

FOLFOX7方案治疗晚期胃肠道肿瘤的疗效观察

目的观察FOLFOX7方案在治疗晚期胃肠道肿瘤中的作用。方法L—OHP 130mg／m^2静脉滴入，2h，d1；CF500mg／m^2静脉滴入，2h，d1；5-Fu2．4—3．0／m^2．Civ．46—48小时，21d重复最少2个疗程后评价疗效。结果24例患者中，完全缓解0例(CR)，部分缓解12例(PR)50％，稳定9例(NC)37．5％、进展4例(PD)16．67％。毒副反映较轻。特殊毒性是外周神经感觉异常，停药消失。骨髓抑制不明显，只有1例为Ⅳ度抑制。较轻微胃肠道反应。结论FOLFOX7方案应用于治疗晚期胃肠道肿瘤有一定疗效，可一定程度提高患者生活质量，且毒副反应轻，较易耐受。     

卡铂在宫颈癌化疗中的应用

全文综述卡铂的药理学特点和毒副反应,主要介绍卡铂用于宫颈癌的同步化疗、新辅助化疗和晚期与复发宫颈癌化疗的临床研究进展.     

草酸铂治疗晚期胃癌疗效观察

目的 :观察草酸铂 (L OHP)联合5 -氟尿嘧啶 ( 5 FU )和甲酰四氢叶酸钙(CF)在治疗晚期胃癌中的作用。方法 :L OHP 13 0mg/m2 静脉滴入 ,持续 2h ,d1;CF 10 0mg/m2 静脉滴入 ,d1～d5,5 FU 3 75mg/m2 静脉滴入 ,d1～d5。 2 1d重复。结果 :2 2例患者中 ,完全缓解 (CR) 1例 ,部分缓解 (PR) 12例 ,稳定 (NC) 5例 ,进展 (PD)4例 ,有效率 (CR PR) 5 9 0 9%。毒副反应均比较轻 ,毒性特点是外周神经感觉异常 ,症状可逆。结论 :L OHP联合 5 FU(CF)方案应用于治疗晚期胃癌可以获得比较高的疗效 ,显著提高患者生活质量     

Release of Cytokines from Human Umbilical Vein Endothelial Cells Treated with Platinum Compounds in vitro

Endothelial cells (EC) produce cytokines, such as interleukin (IL)-1, IL-6, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF). These cytokines have an important role in the proliferation and differentiation of hematopoietic progenitor cells. On the other hand, anticancer agents generally cause hematopoietic disorders. However, little is known about the effects of chemotherapeutic agents on the secretion of cytokines from EC. Therefore, we investigated if treatment with platinum compounds may stimulate EC to secrete cytokines. EC newly isolated from a human umbilical vein were exposed to cisplatin, carboplatin, or TRK-710 for 80 min, then the cells were washed and placed in fresh medium. The levels of cytokines in the fresh medium were measured by the ELISA method, the levels of intracellular hydrogen peroxide (H₂O₂) were measured by flow cytometry, and the rhodamine 123-stained live mitochondria of the EC were observed under a confocal laser microscope. Platinum compounds induced cytokine production in human EC: cisplatin most prominently induced the release of IL-1 and IL-6, and TRK-710 had the greatest ability to induce the release of GM-CSF. Intracellular H₂O₂ production and IL-8 release were transiently induced immediately after treatment with platinum compounds, leading to IL-1 release when H₂O₂ production was eliminated. These results may provide new insights into the hematological toxicity induced by anticancer agents and the role of IL-1 and IL-6 secreted from EC in this toxicity.     

Amelioration of Cisplatin-Induced Ototoxicity in Rats by L-arginine: The Role of Nitric Oxide,Transforming Growth Factor Beta 1 and Nrf2/HO-1 Pathway

Background: Cisplatin is an alkylating agent that inhibits DNA replication and interferes with proliferation of cancer cells. However, the major limiting factor for its use is the possible development of adverse effects, including ototoxicity. Up till now, the mechanisms of this ototoxicity remain poorly understood. However, induction of oxidative stress and activation of the inflammatory cascade were suggested as contributing factors. Purpose: The aim of this study was to explore the effect of L-arginine on cisplatin-induced ototoxicity in rats. Methods: Thirty male adult Wistar rats were divided into three equal groups as follows: control group; cisplatin group and cisplatin + L-arginine group. Auditory brainstem response (ABR), tissue oxidative stress parameters, total nitrate/nitrite, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) content, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and interleukin 15 (IL-15) were assessed. Also, the cochlear tissues were subjected to histopathological and electron microscopic examination. Results: Administration of L-arginine to cisplatin-treated rats induced significant decrease in the average ABR threshold shifts at all frequencies, tissue TGF-β1, TNF-α and IL-15 associated with significant increase in tissue antioxidant enzymes, total nitrate/nitrite and Nrf2/HO-1 content compared to cisplatin group. Also, pretreatment of cisplatin-injected rats with L-arginine induced significant improvement of the histopathological and electron microscopic picture compared to cisplatin group. Conclusion: L-arginine may serve as a promising therapeutic modality for amelioration of cisplatin-induced ototoxicity.