5-氟尿嘧啶或卡培他滨联合奥沙利铂治疗转移性结直肠癌有效性及安全性的Meta分析

目的比较5-氟尿嘧啶（5-Fu）或卡培他滨联合奥沙利铂治疗转移性结直肠癌的临床疗效和安全性。方法以转移性结直肠癌、奥沙利铂、5-Fu、卡培他滨为检索词,查阅2011年6月前发表的有关5-Fu或卡培他滨联合奥沙利铂治疗转移性结直肠癌的随机对照研究。由2名作者各自独立对入选文献中试验设计、研究对象的特征、研究结果等内容按照预先制订的数据表进行摘录。采用RevMan4．2软件进行统计分析。结果按照筛选标准,共有6篇文献入选,全部研究共计2189例转移性结直肠癌患者。两组患者基本特征均衡可比。临床疗效方面,有效率合并相对危险度（RR）为0．92[95％CI（0．82,1．02）,P=0．121,中位无疾病进展生存时间、中位生存时间合并加权均数差（WMD）分别为-0．19[95％CI（-0．73,0．35）,P=0．49],-1．91[95％CI（-2．53,0．16）,P：0．08],综合分析结果两组间均无优劣。Ⅲ～Ⅳ级毒副作用的比较中,中性粒细胞减少的综合分析显示卡培他滨组的发生率显著低于5-Fu组,合并RR为0．24[95％a（0．11,0．55）,P=0．0007],而手足症状发生率高于5-Fu组,合并RR为2．83[95％a（1．66,4．82）,19=0．0001]。结论5-Fu或卡培他滨联合奥沙利铂治疗转移性结直肠癌疗效无优劣。在Ⅲ～Ⅳ级毒性方面中性粒细胞减少在5-Fu组更易发生,卡培他滨组主要以手足症状为主。     

替吉奥联合奥沙利铂一线治疗转移性结直肠癌有效性与安全性的Meta分析#br#

目的 评价替吉奥联合奥沙利铂（SOX）一线治疗转移性结直肠癌（mCRC）的有效性和安全性。方法 通过The Cochrane Library、PubMed、EMBASE和MEDLINE、中国知网（CNKI）、万方数据库等检索SOX方案一线治疗mCRC的多中心随机对照试验（RCT）,用Rev Man 53版软件进行Meta分析。结果 共纳入5项临床多中心RCT,合计1382例mCRC患者。Meta分析结果显示,与奥沙利铂联合其他氟尿嘧啶类化疗药物比较,SOX方案在无进展生存期（HR=0.90,95％CI：0.80～1.02,P=0.10）、总生存期（HR=1.14,95％CI：0.98～1.31,P=0.08）、客观缓解率（RR=1.12,95％CI：0.87～1.43,P=0.38）、疾病控制率（RR=104,95％CI：0.98～110,P=0.24）的差异均无统计学意义。3～4 级不良反应：SOX方案组的白细胞减少发生率低于奥沙利铂联合其他氟尿嘧啶类药物（P＜0.05）,而口腔黏膜反应、厌食、腹泻的发生率高于奥沙利铂联合其他氟尿嘧啶类药物（P＜0.05）,两种方案在中性粒细胞减少、血小板减少、贫血、恶心、呕吐、乏力不良反应的发生率方面差异均无统计学意义（P＞0.05）。结论 OX一线治疗晚期结直肠癌的疗效与奥沙利铂联合其他氟尿嘧啶类药物的疗效相似,不良反应不同,替吉奥有可能成为除卡培他滨外口服氟尿嘧啶类一线治疗晚期结直肠癌的另一种选择。     

奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗结直肠癌肝转移

目的观察奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗结直肠癌肝转移的临床效果和毒副反应。方法入组70例结直肠癌术后多发性肝转移患者,根据治疗方案的不同分为2组,观察组35例给予奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗,对照组35例给予常规奥沙利铂加卡培他滨方案(静脉给药)。结果观察组、对照组有效率分别为68.6%、37.2%,差异有统计学意义(P<0.05);中位生存期分别为14.6、10.8个月,比较差异无统计学意义(P>0.05)。观察组神经毒性、骨髓抑制发生率低于对照组,差异有统计学意义(P<0.05)。结论奥沙利铂加卡培他滨经肝动脉化疗栓塞术治疗结直肠癌肝转移疗效和耐受性均优于奥沙利铂加卡培他滨常规静脉给药。     

全身热疗联合奥沙利铂方案治疗晚期结直肠癌

[目的]评价全身热疗(whole body hyperthermia,WBH)联合奥沙利铂、氟尿嘧啶(5-Fu)、醛氢叶酸(CF)治疗晚期结直肠癌的近期疗效和不良反应.[方法]实验组22例既往单纯化疗方案治疗效果不佳的晚期结直肠癌患者采用全身热疗联合奥沙利铂、5-Fu、CF进行治疗1周期后,再采用奥沙利铂联合5-Fu、CF化疗1周期;对照组27例为同时期就诊患者中随机抽取的未经治疗的晚期结直肠癌患者,采用奥沙利铂联合5-Fu和CF化疗2周期.3周为一个周期,完成2周期化疗后4周评价疗效.[结果]实验组有效率为63.6%,对照组有效率为33.3%;常见毒副反应为胃肠道反应、神经毒性及白细胞减少,但均较轻微.[结论]WBH联合奥沙利铂、5-Fu、CF治疗晚期结直肠癌具有显著的治疗效果,并且毒性可耐受.     

卡培他滨联合奥沙利铂一线治疗老年晚期大肠癌58例

[目的]评价卡培他滨联合奥沙利铂(XELOX方案)一线治疗老年晚期大肠癌的疗效和毒副反应。[方法]58例老年(≥65岁)晚期大肠癌患者,奥沙利铂130mg/m2,第1d静脉滴注;卡培他滨2000mg/(m2·d),每天2次口服,第1～14d,21d为1个周期。[结果]58例患者中CR3例,PR25例,SD14例,PD16例,有效率为48.28%。中位生存期为15.8个月,中位疾病进展时间为8.1个月。毒副反应主要为手足综合征、神经毒性、骨髓抑制、恶心、呕吐多为Ⅰ～Ⅱ度。[结论]卡培他滨联合奥沙利铂的方案疗效确切,毒副反应小,老年患者能耐受,能提高生活质量。     

奥沙利铂联合卡培他滨治疗晚期胃癌的临床观察

目的：探讨奥沙利铂联合卡培他滨治疗晚期胃癌近期疗效。方法：82例晚期胃癌患者随机分为两组,A组采用奥沙利铂＋卡培他滨方案化疗,B组采用顺铂＋5～氟尿嘧啶＋甲酰四氢叶酸化疗,观察其有效率及不良反应。结果：A组有效率为54．55％,B组有效率为28．95％,P〈0．05,两者有显著性差异。且A组的胃肠道反应明显减轻。其他相关不良反应能耐受。结论：奥沙利铂联合卡培他滨方案治疗晚期胃癌疗效较好,不良反应能够耐受,可在晚期胃癌病人中应用。     

希罗达联合奥沙利铂治疗转移性结直肠癌的疗效系统评价

目的对希罗达联合奥沙利铂治疗转移性结直肠癌的临床疗效作系统评价。方法采用奥沙利铂、希罗达、卡培他滨、转移性结肠癌等检索词,查阅2000年至2012年国内外希罗达联合奥沙利铂治疗转移性结直肠癌随机对照试验的相关文献,并进行文献索源和手工检索,降低文献漏检。由2名人员按照预先制定的数据表筛选并摘录文献中试验设计、研究对象特征和研究结果。采用stata 12.0统计软件处理数据。结果共检索文献125篇,按照筛选标准,共7篇纳入研究。meta分析结果显示,研究组有效率为17.60%(161/915),与对照组有效率18.65%(169/906)比较,2组总有效率差异无统计学意义[RR=0.90,95%CI(0.77,1.05),P=0.174]。6个研究组(n=885)的中位生存期标准化均数差SMD=-0.065[95%CI(-0.158,0.028),P=0.173];7个研究(n=915)的中位无疾病生存期准化均数差为SMD=-0.046[95%CI(-0.136,0.045),P=0.323],差异均无统计学意义。结论希罗达联合奥沙利铂治疗转移性结直肠癌临床疗效较好;与氟尿嘧啶联合用药比较,疗效无优劣,可以作为一线治疗药物推荐使用。     

多西紫杉醇联合卡培他滨和奥沙利铂治疗28例晚期胃癌

[目的]观察多西紫杉醇联合卡培他滨、奥沙利铂作为一线方案治疗晚期胃癌的疗效及毒副反应。[方法]对28例晚期胃癌患者采用多西紫杉醇联合卡培他滨、奥沙利铂方案化疗。至少2个周期后评价疗效。按WHO标准评价近期疗效和毒副反应。[结果]可评价疗效者26例,完全缓解(CR)3例,部分缓解(PR)13例,总有效率61.54%。中位达进展时间7.0个月,中位生存期12.8个月。可评价毒性患者28例,毒副反应主要有骨髓抑制,外周神经感觉异常,手足综合征,口腔黏膜炎,恶心、呕吐和腹泻。全组无治疗相关性死亡。[结论]多西紫杉醇联合卡培他滨、奥沙利铂治疗晚期胃癌有较好的疗效,毒副反应可以耐受。     

奥沙利铂在局部进展期直肠癌术前同步放化疗中的应用进展

目前基于氟尿嘧啶及卡培他滨的术前同步放化疗是局部进展期直肠癌的标准治疗模式,但仍有较高的远处转移率,为进一步提高疗效,探索新的化疗药物越来越受到学界的重视.其中奥沙利铂因其在辅助化疗及姑息治疗中的效果卓越,受到越来越多学者的关注,并因此开展了一系列Ⅰ～Ⅲ期临床研究.绝大多数Ⅰ/Ⅱ期临床研究表明奥沙利铂具有很好的应用前景,不仅达到良好病理完全缓解(pCR)率及肿瘤降期率,且不良反应可耐受.但是,在Ⅲ期临床研究中,STAR-01、ACCORD-12、NSABP-R04、PETACC-6均为阴性结果,仅CAO/ARO/AIO-04是阳性结果,显示奥沙利铂组能够获得显著的总生存期(DFS)获益,故奥沙利铂能否应用于局部进展期直肠癌术前放化疗存在明显的争议.因此根据目前研究结果,在直肠癌术前新辅助放化疗中,仍然不推荐在5-Fu/卡培他滨基础上常规使用奥沙利铂.全文对奥沙利铂在局部进展期直肠癌术前同步放化疗中的应用进行了总结,希望为进一步的临床研究提供依据.     

奥沙利铂联合卡培他滨治疗胃癌术后淋巴转移的近期疗效

[目的]探讨奥沙利铂联合卡培他滨治疗胃癌手术后淋巴转移的近期疗效。[方法]48例胃癌手术后淋巴转移患者采用奥沙利铂联合卡培他滨方案治疗共176个周期。[结果]CR4例，PR28例，NC12例和PD4例，总有效率（CR＋PR）为66．7％f32／48）。中位缓解期6．2个月，中位生存期12.3个月，1年生存率为60．5％，临床受益者共44例（90．5％）。毒副反应可耐受，无患者因为毒副反应终止治疗，无相关死亡出现。[结论]奥沙利铂加卡培他滨方案治疗胃癌手术后淋巴转移疗效较好。毒副反应能够耐受。可作为一线方案在胃癌手术后淋巴转移的病人中应用。     

Oxaliplatin

Oxaliplatin (L-OHP) is a new third generation 1,2-DACH-platinum derivative. Pre-clinical studies from human cell lines suggested that L-OHP was efficacious in treating advanced or recurrent colorectal cancer. Furthermore, L-OHP and fluorouracil combination was shown to be synergistic both in experimental studies and in clinical trials. Toxicity profiles also differ from other platinum derivatives. Neurotoxicity is much more frequent, but renal toxicity, alopecia, and ototoxicity are less. Combination chemotherapy with L-OHP, infusional 5-fluorouracil, and leucovorin-a treatment regimen known as FOLFOX, has been shown clinical benefit in response rate, time to progression, and overall survival as compared to those achieved with 5-fluorouracil+leucovorin. Thus, introduction of irinotecan and L-OHP into clinical use has been a major advances for patients with metastatic colorectal cancer. Additional research must be required to define optimal dose schedule and sequence of these agents. Inducing remission with first-line treatment has been shown a significant correlation between tumor response and survival (progression free and overall).     

Oxaliplatin Neurotoxicity

Oxaliplatin (OXA) is a first-line agent in the systemic treatment of colorectal cancer (CRC). OXA-induced neuropathy is the most prominent adverse effect, both during and after the completion of chemotherapy. OXA neurotoxicity (OXA-NTX) is a dose-limiting, frequent, and long-lasting adverse event that may compromise therapeutic outcome and the quality-of-life of CRC patients. Increased knowledge of the pathophysiology and clinical profile of this neuropathy is being achieved. Two types of neuropathy are usually observed, and evidence suggests a link between the acute symptoms and the development of chronic NTX. In this paper we review the main advances and the outstanding issues concerning OXA-NTX, for example calcium/magnesium and other drugs in the prophylaxis and treatment of this neuropathy. Recently available and ongoing investigation of pharmacogenomics, clinical and neurophysiological risk factors, and early markers of OXA-NTX are of great value in clinical decision-making, contributing to minimizing the risk of severe neuropathy.     

Oxaliplatin neurotoxicity

Oxaliplatin is a reference drug in the treatment of digestive-tract tumors, especially colorectal cancer. Its toxicity profile is dominated by a peripheral sensitive neuropathy, with neuromuscular manifestations. This neurotoxicity has 2 components: an acute toxicity characterized by a rapid onset of cold-induced distal dysesthesia and/or paresthesia, muscular contractions, numbness, stiffness, usually transient but able to evolve into a chronic, persistent sensory peripheral neuropathy that eventually causes functional impairment. A persistent sensory peripheral neuropathy may develop with prolonged treatment, eventually causing superficial and deep sensory loss, sensory ataxia and functional impairment. This neurotoxicity is frequent, 80%of the patients and becomes chronic in 15 to 20%of the patients, sometimes irreversible. The mechanism of this neurotoxicity has been elucidated: an increased neuronal excitability is due to the action of oxaliplatin on voltage-gated sodium channels through chelation of calcium by the oxaliplatin metabolite. The prevention of this neurotoxicity is a major goal, taking in account the wide indications of this drug. Different approaches have been or are evaluated, based on pathogenic or practical concepts: 1) modifications of the administration schedule; 2) substances acting upon sodium channels : calcium-magnesium, carbamazepine, gabapentine, venlafaxin; 3) detoxifying agents and antioxydants: glutathion, amifostine, alphalipoic acid, tocopherol ; 4) substances used in other kinds of neuropathy: glutamine, alphalipoic acid; 5) neurotrophic factors: NGF, LIF; 6) oxaliplatin analogs, with a DACH platin, without oxalate. Calcium-magnesium infusion seem to be an efficient and safe approach. Further studies are necessary for a better understanding and prevention of this neurotoxicity, potentially severe.     

Oxaliplatin and ovarian cancer

Oxaliplatin was brought into clinical evaluation in ovarian cancer because of the in vitro and in vivo antitumor activity observed in experimental models resistant to cisplatin. As single agent at 130 mg/m2 every 3 weeks, the objective response rates rage from 16% to 29% in patients treated after failure of one or two regimens. As first line, in a randomized trial cyclophosphamide-cisplatin versus cyclophosphamide-oxaliplatine, no significant statistical differences were observed in efficacy parameters (response rate, progression free survival and overall survival). The toxicity profile seemed to favor the oxaliplatin arm. Many associations with other available active drugs as taxanes, gemcitabine and liposomal doxorubicin were performed with promising results.     

多西紫杉醇联合奥沙利铂、卡培他滨与FOL FOX4 方案治疗晚期胃癌疗效比较

 目的 观察多西紫杉醇联合奥沙利铂、卡培他滨方案与FOLFOX4方案治疗晚期胃癌的客观疗效，疾病进展时间和毒性反应。方法 治疗组41例晚期胃癌患者接受多西紫杉醇25mg／m²（d1，d8，d15），奥沙利铂60mg／m^2（d1，d8，d15），卡培他滨每日1250mg／m²，分2次口服，d1～14，28d为1周期，疗程2～6周期。对照组40例晚期胃癌患者接受奥沙利铂85mg／m^2d1，亚叶酸钙200mg／m²（2h静脉输注）d1-d2，而后5-Fu400mg／m²（10min静脉推注）及5-Fu600mg／m²（持续静脉泵入22h），d1～d2，每14d重复，2次为1周期。结果 多西紫杉醇联合奥沙利铂、卡培他滨方案治疗组总有效率为58．5％，中位疾病进展时间（TTP）为6．8个月。常见的毒性反应为白细胞和中性粒细胞减低，手足综合征和周围神经毒性反应等。FOLFOX4方案总有效率为47．4％，中位TTP为5．9个月。常见的毒性反应为白细胞和中性粒细胞减低和周围神经毒性反应等。结论 多西紫杉醇联合奥沙利铂、卡培他滨化疗方案治疗晚期胃癌近期疗效显著，耐受性较好。     

Oxaliplatin and genito-urinary tumors

Considering genito-urinary tumors, the use of oxaliplatin should be restricted to clinical trials since no marketing approval has been obtained. Results of prospective studies currently suggest that the development of oxaliplatin should be carried on with first-line management of poor prognosis metastatic germ cell tumors as well as metastatic bladder cancer patients not eligible for cisplatin therapy.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期胃癌的研究

目的：研究奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗进展及转移性胃癌的疗效和毒副反应。方法：采用奥沙利铂130mg／m^2，静滴2小时，第1天；亚叶酸钙200mg／m^2，静滴2小时，第1～5天；氟尿嘧啶300mg／m^2，静滴4小时，第1～5天(亚叶酸钙滴完后用)；21天或28天为1周期，行4周期治疗后判定疗效。结果：其中完全有效3例(8．8％)，部分有效11例(32．4％)，无变化14例(41．2％)，进展6例(17．6％)，总有效率为41．2％，中位总生存期9个月。毒副反应以骨髓抑制、感觉性神经毒性为主，其中白细胞减少占44．1％，血小板减少占41．2％。感觉性神经毒性占82．4％，无化疗相关死亡。结论：奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期胃癌疗效肯定，毒副反应能耐受，值得进一步试用。     

Oxaliplatin in non-seminomatous germ-cell tumors

Recently, Kollmannsberger et al. [1] reported the final resultsof a phase II trial of oxaliplatin as a single agent in patientswith relapsed or refractory non-seminomatous germ-cell tumors(NSGCT) treated from 1998 to 2001. The authors concluded thatoxaliplatin is an active agent and     

奥沙利铂联合5-氟脲嘧啶/亚叶酸钙治疗晚期胃癌临床研究

目的:研究奥沙利铂联合5-氟脲嘧啶/亚叶酸钙治疗进展期胃癌的临床疗效及毒副反应.方法:将66例晚期胃癌患者随机分成两组,研究组33例,奥沙利铂130rmg/m2,静滴3小时,第一天给药;亚叶酸钙100mg,静滴2小时,第1～5天给药;5-氟脲嘧啶600mg/m2,微量泵持续静脉灌注22小时,第1～5天给药.对照组33例,顺铂30mg/m2,静脉滴注,第1～3天给药,亚叶酸钙和5-氟脲嘧啶用药方法同研究组.每3～4周为一周期.结果:研究组与对照组近期有效率分别为54.5%与42.4%,两组比较无统计学差异(P＞0.05);研究组1年生存率及中位生存期均优于对照组,但无统计学差异(P＞0.05);消化道反应发生率研究组低于对照组(P＜0.05);外周神经毒性反应发生率研究组高于对照组(P＜0.01).结论:研究组近期疗效、1年生存率及中位生存期均优于对照组,且消化道反应发生率明显低于对照组,值得临床进一步观察研究.