2012年常见恶性肿瘤治疗及其相关研究新进展

恶性肿瘤治疗进步依赖于针对新药或新方法的多中心Ⅲ期临床试验结果，下面分述2012年发表的恶性肿瘤治疗、筛查、预后和疗效监测临床研究的重要结果。
　　一、化学治疗和靶向治疗
　　1．培美曲塞联合卡铂治疗能延长体力状况不佳的晚期非小细胞肺癌（ non-small cell lung cancer ，NSCLC）的总生存期和无进展生存期［1］：体力状况不佳者指 ECOG 体力评分2分的晚期NSCLC者。与培美曲塞单药比较，联合化疗提高有效率（ overall response rate，ORR）（24％ vs．11％）；延长总生存期（overall sur-vival，OS）（9.1个月 vs．5.6个月）和无进展生存期（progression-free survival，PFS）（5.9个月 vs．3.0个月）；提高12个月时OS （43％vs．18％；HR 0.57）和PFS（18％ vs．4％；HR 0.46）。联合化疗3或4级血液毒性增加：贫血（12％vs．4％），嗜中性白细胞减少症（6％vs．1％），血小板减少（1％vs．0％）。因此，结合其他研究，对于不含酪氨酸激酶抑制剂（ tyrosine kinase inhibitor ，TKI）靶点的晚期NSCLC能耐受双药化疗者，推荐双药化疗。单药化疗是不能耐受双药化疗者的选择。

OBJECTIVE: This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hal ucination of patients with schizophrenia spectrum disorders.
DATA SOURCES: Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Control ed Trials databases from January 1985 to May 2012. Key words were “transcranial magnetic stimulation”, “TMS”, “repetitive transcranial magnetic stimulation”, and “hal ucination”.
STUDY SELECTION: Selected studies were randomized control ed trials assessing therapeutic ef-ficacy of repetitive transcranial magnetic stimulation for hal ucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hal ucination in schizophrenia spectrum disorders. Control groups received sham stimulation.
MAIN OUTCOME MEASURES: The primary outcome was total scores of Auditory Hal ucinations Rating Scale, Auditory Hal ucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hal ucination item, and Hal ucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function.
RESULTS: Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. Al data were completely effective, involving 398 patients. Overal mean weighted effect size for repeti-tive transcranial magnetic stimulation versus sham stimulation was statistical y significant (MD =-0.42, 95%CI: -0.64 to -0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P =0.005). No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for positive or negative symptoms. Compared with sham stimulation, active repeti-tive transcranial magnetic stimulation had equivocal outcome in cognitive function and commonly caused headache and facial muscle twitching.
CONCLUSION: Repetitive transcranial magnetic stimulation is a safe and effective treatment for auditory hal ucination in schizophrenia spectrum disorders.

Her-2阳性的复发转移性乳腺癌(MBC)的一线治疗进展

乳腺癌是全世界女性常见的恶性肿瘤,尽管早期治疗效果较好,但迄今为止,复发转移性乳腺癌(metastatic breast cancer,MBC)仍是不可治愈的疾病,临床Ⅳ期乳腺癌患者的5年总生存率(OS)不足25％[1,2].人类表皮样生长因子受体(Her-2)作为乳腺癌的不良预后因子,同时也是靶向治疗的重要靶点[3].在15％ ～20％的复发转移性乳腺癌(MBC)中存在Her-2扩增或高表达,Her-2阳性的复发转移性乳腺癌具有预后差、OS低和无疾病生存时间(disease free survival,DFS)较短的特点.对于这类患者采用曲妥珠单抗(Trastuzumab,商品名赫赛汀(R))为基础的联合治疗可以提高的总体反应率(overall response rate,ORR),获得更长的OS和至进展生存时间(time to disease to progession,TTP),目前已成为一线的标准治疗方案[4].然而,其他新的分子靶向治疗药物及新的治疗策略也被证明具有一定前景,本文就近年来Her-2阳性的复发转移性乳腺癌(MBC)的一线治疗进展做简要综述.

用兰索拉唑治疗消化性溃疡出血的临床疗效观察

目的：评价用兰索拉唑治疗消化性溃疡出血的临床疗效。方法：将2012年2月至2014年2月我院收治的101例消化性溃疡出血患者随机分为治疗组（50例）和对照组（51例）。为治疗组患者使用兰索拉唑进行治疗，为对照组患者使用奥美拉唑进行治疗，并对比分析其临床疗效。结果：治疗组患者治疗的总有效率为98%（显效42例，有效7例，无效1例）。对照组患者治疗的总有效率为98.04%（显效44例，有效6例，无效1例）。两组患者治疗的总有效率相比较差异不显著（P＞0.05），无统计学意义。在治疗的过程中，两组患者均未发生明显的不良反应。结论：在治疗消化性溃疡所致上消化道出血方面，兰索拉唑和奥美拉唑疗效相当，但其引发的不良反应更轻微，值得在临床上推广使用。

595nm脉冲染料激光治疗鲜红斑痣1560例临床研究

目的 评价595 nm脉冲染料激光治疗不同年龄段鲜红斑痣患者的临床疗效和不良反应.方法 应用美国Candela公司生产的595 nm脉冲染料激光治疗鲜红斑痣1560例,根据患者年龄、皮损类型等采用不同参数进行激光照射治疗.结果 595 nm脉冲染料激光治疗鲜红斑痣总有效率为76.73％(1197/1560),疗效与患者年龄、皮损类型等因素关系密切,不良反应发生率低,且耐受性好.结论 595 nm脉冲染料激光治疗鲜红斑痣安全有效.

强脉冲光与红光治疗糖皮质激素依赖性皮炎临床疗效分析

目的 回顾性分析比较强脉冲光与红光治疗糖皮质激素(简称激素)依赖性皮炎的临床疗效及不良反应.方法 应用强脉冲光治疗以面部毛细血管扩张为主要表现的激素依赖性皮炎患者70例,能量密度20～23 J/cm2,其中脉宽为2.6～5.0 ms,延迟时间为15 ～ 20 ms,间隔4周治疗1次,平均3.49次.使用波长(633±3)nm红光治疗以面部皮肤敏感为主要表现的激素依赖性皮炎患者197例,能量密度128J/cm2,每次照射20 min,每周治疗2次,平均4.23次.对每次治疗的疗效及不良反应进行评价.结果 强脉冲光治疗激素依赖性皮炎的总有效率为88.57％；红光治疗的总有效率为83.76％.强脉冲光3脉冲治疗组和2脉冲治疗组的疗效差异有统计学意义(x2=8.14,P＜0.05).所有患者均未出现严重不良反应.结论 强脉冲光和红光治疗激素依赖性皮炎均有较好疗效.

0.1％他克莫司软膏不同疗程治疗面部糖皮质激素依赖性皮炎的临床观察

目的 观察0.1％他克莫司软膏不同疗程治疗面部糖皮质激素依赖性皮炎的临床疗效、安全性以及治疗结束后的病情反跳情况.方法 将104例面部糖皮质激素依赖性皮炎患者随机分为3组,均给予0.1％他克莫司软膏外涂,每日2次,疗程分别为4周、8周、16周,比较3组的疗效.疗程结束后4周随访比较3组的反跳情况.结果 共90例患者完成临床研究,其中疗程4周组32例、疗程8周组29例、疗程16周组29例,总有效率分别为75.00％、82.76％及86.21％,3组间有效率差异无统计学意义.3组的反跳率分别为46.88％、41.38％及20.69％,疗程16周组与疗程4周组、疗程8周组比较,差异均有统计学意义；疗程4周组与疗程8周组比较,差异无统计学意义.31.73％患者局部有刺激反应,均发生在治疗第1周.结论 0.1％他克莫司软膏治疗面部糖皮质激素依赖性皮炎安全、有效,疗程延长,总有效率上升不明显,疗程4周即能获得明显而稳定的疗效.但疗程越长,治疗结束后的反跳率越低.

两种糖皮质激素注射液皮损内注射治疗活动期斑秃的临床疗效观察

目的 比较复方倍他米松注射液和醋酸曲安奈德注射液皮损内注射治疗活动期斑秃的临床疗效.方法 将160例活动期斑秃患者随机分成两组,治疗组100例、对照组60例,治疗组用复方倍他米松注射液皮损内注射,对照组用醋酸曲安奈德注射液皮损内注射,每3周1次,12周后观察结果.结果 治疗12周后治疗组痊愈60例(60.0%),显效32例(32.0%),总有效率92.0%;对照组痊愈25例(41.7%),显效19例(31.67%),总有效率73.3%;治疗组有效率和痊愈率显著高于对照组(χ2值分别为10.25和5.06,P<0.01和<0.05).治疗组出现局部头皮萎缩8例(8%),局部毛囊炎8例(8%);对照组出现局部头皮萎缩9例(15%),局部毛囊炎3例(5%),两组不良反应发生率比较,差异无统计学意义(P>0.05).结论 复方倍他米松注射液皮损内注射治疗活动期斑秃疗效显著.

从EGFR基因突变看肺癌异质性

目前,肺癌依然是导致人类因肿瘤所致死亡的首位疾病,全球每年因肺癌死亡的人数超过100万.其中80％是非小细胞肺癌(non-small cell lung cancer,NSCLC),60％～70％的NSCLC患者就诊时已经失去根治性手术的机会.对于这部分患者,目前的标准治疗仍为含铂双联化疗,其客观缓解率(objective response rate,ORR)为15％～36％,总生存期(overall survival,OS)一般为8～10个月,1年生存率通常不超过30％～40％,5年生存率仅为10％～15％.

吉西他滨治疗RRM1阴性晚期难治非小细胞肺癌患者1例

目前吉西他滨/铂类方案是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的标准治疗方法之一.Anderson等[1]报告吉西他滨单药治疗NSCLC客观缓解率(objective response rate,ORR)为20%;国内管忠震等[2]报道吉西他滨联合顺铂方案的疾病控制率为56.1%,部分缓解率为43.9%,中位缓解时间(174±18.5)天.

1 IntroductionCisplatin-based combination chemotherapy using one of the novel cytotoxic agents, such as gemcitabine or taxane, prolongs survival of patients with advanced non-small cell lung cancer (NSCLC). The recent published phase Ⅲ study that compared paclitaxel/cisplatin to gemcitabine/cisplatin, docetaxel/cisplatin or paclitaxel/carboplatin has shown equal efficacy with the exception of longer progression-free survival from the gemcitabine/cisplatin combination[1]. Overall tumor response rates of 1 155 eligible patients was 19% with median survival of 7. 9months only. Findings from other major randomized comparative studies were similar. Table 1 summarized the tumor response rate and survival of these studies[1-4]. Hundreds of patients received platinumbased new drug doublets and the overall response rate was persistently reported at only about 20% to 30%. Survivals were better than the first generation of combination chemotherapy but the best median survival was less than 10 months and 1-year survival rate was persistently less than 45 %.

1 IntroductionRecent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).