老年非小细胞肺癌患者药物治疗研究进展

肺癌是目前世界上发病率最高的恶性肿瘤之一,然而,老年患者在临床研究中的代表性不足,导致缺乏指导治疗决定的证据。目前,辅助性化疗通常被推荐用于IB～III 期非小细胞肺癌（NSCLC）手术切除术后治疗,老年晚期NSCLC 患者的治疗方案则主要为单药化疗以及以铂类为基础的联合化疗。此外,靶向治疗及免疫靶向治疗成为新的研究方向。本文主要对辅助化疗及老年晚期NSCLC 患者的药物治疗相关临床研究证据进展进行综述。     

老年非小细胞肺癌化疗研究进展

近年来老年非小细胞肺癌 （non-small cell lung cancer,NSCLC）的发病率和死亡率逐年增加.大于 70岁的 NSCLC患者无论在临床分期、表现、病理特点以及状态评分 （performance status,PS）上,与小于 70岁的 NSCLC患者相似.由于大于 70岁的 NSCLC患者往往合并慢性基础疾病,在化疗耐受性和生理功能上明显降低.因此,老年 NSCLC患者的化疗具有特殊性,其中包括了以第三代化疗药物为主的单药化疗.非铂类药物为主和铂类药物为主的联合化疗以及靶向治疗等.     

老年晚期肺癌三线化疗的临床疗效和不良反应观察

目的：探讨老年晚期非小细胞肺癌（ non-small cell lung cancer ,NSCLC）三线化疗的方案、疗效及不良反应。方法回顾性分析2012年1月-2014年4月在接受三线化疗的42例年龄超过70岁的老年晚期NSCLC患者,其中22例采用多西紫杉醇、脂质体紫杉醇、培美曲塞单药化疗,另20例采用含铂联合两药,观察两组近期疗效和不良反应。结果全组总有效率为16．7％,临床获益率为31％,单药化疗组总有效率为13．6％,临床获益率为22．7％,含铂联合化疗组总有效率为20％,临床获益率为40％,两组比较差异有统计学意义（P＜0．05）;两组化疗过程中毒副反应主要为脊髓抑制（白细胞下降、血小板下降）,其次为消化道反应（恶心、呕吐）,部分患者出现肝、肾功能损伤,治疗期间均未发生因不良反应而导致的死亡,两组不良反应发生率比较均无统计学差异（ P＞0．05）。结论老年晚期NSCLC三线化疗的临床疗效适中,化疗不良反应可耐受,若患者体力评分较好可采用两药联合化疗,使用两药的疗效优于单药。     

非小细胞肺癌的靶向治疗

肺癌发病率、死亡率均居高位,其中非小细胞肺癌（NSCLC）占肺癌的80～85%,30～40%的NSCLC在诊断时即属于晚期,失去手术机会[1],尽管含铂方案的化疗能一定程度上延长晚期NSCLC患者的生存期,但疗效有限,目前已有诸如培美曲赛或厄罗替尼（EGFR-TK Is）的靶向治疗及靶向联合化疗的新治疗途径[2-5]。本文就近年来NSCLC的靶向药物及治疗做一综述。     

多西他赛不同给药方案治疗非小细胞肺癌的效果

目的:综述多西他赛不同给药方案治疗晚期非小细胞肺癌的优化效果。方法:汇总多西他赛单药和联合方案单周和3周方案一线和二线治疗晚期非小细胞肺癌(NSCLC)20个大型临床试验,比较多西他赛不同给药周期的不同方案的生存期(率)、生活质量和药物安全性的效果。结果:①Ⅳ期非小细胞肺癌患者[躯体功能评分(PS)为1～2]的老年病人(>75岁),一线治疗可选用多西他赛单药3周方案,二线治疗可选多西他赛单药每周方案。②Ⅳ期非小细胞肺癌患者(PS评分为0～1),如果基因ERCC1 mRNA表达水平低(或无ERCC1数据),可选择多西他赛联合顺铂3周方案。③Ⅳ期非小细胞肺癌患者,如果ERCC1高表达,可选择多西他赛联合吉西他滨方案治疗。④Ⅳ期非小细胞肺癌患者(PS评分为1～2)的病人(<75岁),可考虑选用多西他赛联合顺铂的每周方案。结论:多西他赛针对不同患者化疗组合,给药计划和化疗剂量的个体化选择将是晚期非小细胞肺癌的治疗所必需的。     

晚期非小细胞肺癌维持治疗进展

非小细胞肺癌(NSCLC)是全球范围内最常见的恶性肿瘤之一。尽管含铂两药联合方案以及靶向药物适度提高了晚期NSCLC的疗效,其总体预后仍差。维持治疗是目前晚期NSCLC研究的热点,其目的是希望通过维持治疗进一步改善患者预后。本文通过目前已知的Ⅲ期临床研究探讨晚期NSCLC维持治疗的优势和药物选择。     

老年晚期非小细胞肺癌化疗方案的临床分析

目的探讨老年晚期非小细胞肺癌(NSCLC)的化疗方案选择。方法对我院2000年6月至2007年6月收治的有完整资料85例(年龄≥70岁)老年非小细胞肺癌患者分为单药化疗组、铂类为基础的联合化疗两组,对其临床资料、治疗效果及不良反应进行回顾性对照分析。结果单药化疗组21例,铂类为基础的联合化疗64例。单药化疗组心、肝、肾等基础疾病合并率(100%)明显高于联合化疗组(P<0.05)。铂类联合化疗组RR(39.1%),明显高于单药化疗组(23.8%)。铂类联合化疗组中位生存期(MST)11.5个月、疾病进展时间(TTP)7.4个月、1年生存率(38.3%)、2年生存率(18.5%)均显著高于单药化疗组(P<0.05)。Ⅲ～Ⅳ度副反应发生率明显高于单药化疗组(P<0.05),两组均未出现化疗相关死亡。结论高龄并非化疗禁忌,一般情况良好的老年晚期NSCLC患者可考虑选择铂类为基础的联合方案化疗,一般情况较差者,可行单药化疗。     

老年晚期非小细胞肺癌免疫治疗策略

以免疫检查点抑制剂(ICIs)为代表的免疫治疗显著改变了非小细胞肺癌(NSCLC)患者的治疗现状,并已成为所有分期NSCLC的重要治疗手段,但有关老年晚期NSCLC患者的免疫治疗策略亟待进一步明确。通过评估临床研究中老年晚期NSCLC患者的生存数据,该文作者认为在体能状态(PS)评分<2的老年晚期NSCLC患者中使用ICIs单药、ICIs双药联合、ICIs联合化学治疗等方案,能获得与年轻患者相近的生存获益和耐受性;但随着年龄继续增长(尤其是≥80岁),疗效降低且免疫相关毒副反应发生率逐步增加,因此高龄晚期NSCLC患者应慎重选择ICIs治疗。此外,相较于年龄,PS评分才是导致患者无法接受免疫治疗以及较差生存结局的关键因素。总之,老年晚期NSCLC患者的免疫治疗极具挑战性,该领域仍有大量问题需要探索和解决。     

靶向药物联合化疗治疗晚期非小细胞肺癌的临床分析

目的 分析研究靶向药物联合化疗治疗晚期非小细胞肺癌（NSCLC）的疗效.方法 选取2011-2012年我院收治的晚期NSCLC患者46例,将其随机划分为两组.甲组采用常规的化疗药物治疗,乙组在给予常规化疗基础上使用靶向药物治疗,比较两组治疗效果.结果 甲组临床疗效优于乙组,差异有统计学意义（P＜0.05）;两组患者血红蛋白、血小板、白细胞下降及皮疹、消化道反应发生率比较差异无统计学意义（P＞0.05）.结论 给予晚期NSCLC患者采用靶向药物联合化疗治疗,可显著提高临床治疗效果.     

非小细胞肺癌靶向治疗药物临床评价

非小细胞肺癌(NSCLC)患者的中位生存时间仅为8～11月,1年生存率为30%.以铂类药物为基础的联合化疗并不能显著改善晚期NSCLC患者的预后,通过表皮生长因子(EGF)和血管内皮生长因子(VEGF)信号转导通路发挥作用的分子靶向药物治疗可以带来临床获益.本文回顾NSCLC分子靶向药物治疗的最新进展,并重点关注EGF...     

Combination therapy versus single agent chemotherapy in non-small cell lung cancer

There is proven evidence of improved symptom control with platinum-based chemotherapy in the palliation of non-small cell lung cancer, and small but definite improvements in progression-free and overall survival when compared with best supportive care. The newer chemotherapy agents vinorelbine, gemcitabine, docetaxel and paclitaxel all have single agent activity, and in combination with cisplatin these provide superior quality of life and/or survival compared with the single agents, albeit with some increase in haematological toxicity. Doublet chemotherapy consisting of a new agent combined with platinum, cisplatin by preference where tolerated, has become the standard of care for advanced disease. The use of a functional assessment of fitness, rather than chronological age alone, is appropriate in the treatment of elderly patients. Although in this group there is evidence that doublets are superior to single agents, treatment should be undertaken with caution. In the second line setting where patients are unlikely to tolerate combination therapy, single agents have proven superiority over best supportive care. Patients with poor performance status (PS2) without comorbidity may tolerate combination therapy, but currently available evidence is insufficient to allow a definitive recommendation for combination or single-agent chemotherapy.     

Combination therapy versus single agent chemotherapy in non-small cell lung cancer

There is proven evidence of improved symptom control with platinum-based chemotherapy in the palliation of non-small cell lung cancer, and small but definite improvements in progression-free and overall survival when compared with best supportive care. The newer chemotherapy agents vinorelbine, gemcitabine, docetaxel and paclitaxel all have single agent activity, and in combination with cisplatin these provide superior quality of life and/or survival compared with the single agents, albeit with some increase in haematological toxicity. Doublet chemotherapy consisting of a new agent combined with platinum, cisplatin by preference where tolerated, has become the standard of care for advanced disease. The use of a functional assessment of fitness, rather than chronological age alone, is appropriate in the treatment of elderly patients. Although in this group there is evidence that doublets are superior to single agents, treatment should be undertaken with caution. In the second line setting where patients are unlikely to tolerate combination therapy, single agents have proven superiority over best supportive care. Patients with poor performance status (PS2) without comorbidity may tolerate combination therapy, but currently available evidence is insufficient to allow a definitive recommendation for combination or single-agent chemotherapy.     

Paclitaxel: a hope for advanced non-small cell lung cancer?

Recent studies have shown that paclitaxel (Taxol); Bristol-Myers Squibb Co., Princeton, NJ) is an active agent in the treatment of advanced non-small cell lung cancer (NSCLC). Early trials in patients with advanced NSCLC utilised a 24 h infusion schedule and reported objective tumour responses in 21 - 24% of patients. Shorter infusion schedules have equivalent efficacy, and combined results from 14 separate trials of single agent paclitaxel in advanced NSCLC show an overall tumour response rate of 26%. Alternative schedules of paclitaxel from the traditional regimen every three weeks are under active investigation, but it is premature to assess whether these will yield improved efficacy for patients with advanced NSCLC. A single multicentre randomised trial of paclitaxel versus best supportive care in advanced NSCLC showed a significant survival advantage for the chemotherapy arm. Two large randomised Phase III trials have shown that paclitaxel and cisplatin is modestly more effective than cisplatin and podophyllotoxin combinations. The addition of cisplatin or carboplatin to paclitaxel results in higher response rates than for each of the drugs as single agents, but it is unclear whether the combinations yield superior survival or quality of life compared to single agent paclitaxel, or to other paclitaxel-containing regimens.     

Chemotherapy of non-small cell lung cancer in elderly patients

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed over the age of 65 and approximately one-third of all patients with non-small cell lung cancer (NSCLC) are over the age of 70. Elderly patients tolerate chemotherapy poorly as compared to their younger counterparts, because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy, the standard medical treatment of advanced NSCLC. At present, for early stages of the disease there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemo-radiotherapy in locally advanced disease increases toxicity and seems to determine no survival advantage as compared to the radiation therapy alone. In advanced disease, single agent vinorelbine has proven to be active and well-tolerated, and compared to best supportive care, improves survival and perhaps even the quality of life. Gemcitabine is active and well tolerated as well. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared to single agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single agent chemotherapy should remain the standard treatment. The two main research-lines to be explored in the near future are the introduction of biological agents in the treatment schemes and the development of specifically designed schedules of cisplatin-based regimens. However, practicing a multidimensional geriatric awsessment for individualized treatment choice in NSCLC elderly patients is mandatory.     

老年非小细胞肺癌的化疗现状与进展

通过相关文献资料分析老年人小细胞肺癌化疗的必要性,介绍第3代抗肿瘤药物和不同化疗方案的疗效,以及分子靶向治疗药物(如gefitinib)在老年人中的研究进展,为老年人肺癌化疗方案的选择提供参考.     

Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer

Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under-represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co-morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged≥70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged>80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy. Thus, the new paradigm of treatment of elderly patients with advanced NSCLC and a PS score of 0-2 should now be monthly carboplatin with weekly paclitaxel. While there have been no trials of second-line therapy for NSCLC specifically in elderly patients, exploratory subgroup analyses indicate that docetaxel, pemetrexed and erlotinib may provide outcomes in elderly patients similar to those reported in younger patients. However, specific second-line therapy trials in elderly patients are required as the elderly patients in trials conducted to date were probably highly selected to fit the inclusion criteria. There is no more room for nihilism in the treatment of elderly patients with advanced NSCLC. Such patients should be evaluated carefully by geriatric indexes and, if they have a PS score of 0-2, may be treated with platinum-based (mostly carboplatin) doublet therapy in the same manner as their younger counterparts. The optimal second line treatment remains to be determined.     

Taxanes for advanced non-small cell lung cancer

The emergence of novel chemotherapeutic agents with promising anticancer activity in non-small cell lung cancer (NSCLC) during the 1990s has led to an expanded role for chemotherapy in the management of this disease. The taxanes (paclitaxel and docetaxel) are novel microtubule stabilising agents, and have become an integral part of several commonly-used chemotherapy regimens in NSCLC. Taxanes inhibit the growth of lung cancer cell lines, exhibit synergistic interaction with other chemotherapy agents and enhance the efficacy of radiation in vitro. When used in low doses (metronomic dosing), they have important antiangiogenic properties. Several Phase II and III clinical trials have established the efficacy of the taxanes, as single agents and when used in combination with a platinum compound, in the treatment of advanced NSCLC. The use of a taxane in combination with a platinum compound has become an acceptable standard for patients with advanced or metastatic NSCLC. In addition to its efficacy in the first-line therapy of NSCLC, docetaxel is also the FDA-approved second-line agent for recurrent or relapsed NSCLC in the US. Several ongoing trials are comparing the efficacy of combining molecularly targeted agents with taxane-based regimens for the treatment of advanced NSCLC.     

Taxanes for advanced non-small cell lung cancer

The emergence of novel chemotherapeutic agents with promising anticancer activity in non-small cell lung cancer (NSCLC) during the 1990s has led to an expanded role for chemotherapy in the management of this disease. The taxanes (paclitaxel and docetaxel) are novel microtubule stabilising agents, and have become an integral part of several commonly-used chemotherapy regimens in NSCLC. Taxanes inhibit the growth of lung cancer cell lines, exhibit synergistic interaction with other chemotherapy agents and enhance the efficacy of radiation in vitro. When used in low doses (metronomic dosing), they have important antiangiogenic properties. Several Phase II and III clinical trials have established the efficacy of the taxanes, as single agents and when used in combination with a platinum compound, in the treatment of advanced NSCLC. The use of a taxane in combination with a platinum compound has become an acceptable standard for patients with advanced or metastatic NSCLC. In addition to its efficacy in the first-line therapy of NSCLC, docetaxel is also the FDA-approved second-line agent for recurrent or relapsed NSCLC in the US. Several ongoing trials are comparing the efficacy of combining molecularly targeted agents with taxane-based regimens for the treatment of advanced NSCLC.     

康艾注射液联合DP方案治疗晚期非小细胞肺癌对照研究

目的观察康艾注射液联合多西他赛和顺铂治疗晚期非小细胞肺癌（NSCLC）的临床疗效和不良反应。方法70例晚期NSCLC患者分为联合康艾注射液化疗组（40例）和单化疗组（30例）,观察2组患者化疗2个疗程后有效率（RR）及临床获益率（cB）、化疗期间及化疗后2组患者毒副作用观察及生存质量的改善情况。结果联合康艾注射液化疗组有效率及临床获益率均略高于单化疗组,差异有统计学意义（P〈0．05）。康艾＋化疗组化疗毒副反应在胃肠道反应、骨髓抑制、脱发及疲劳方面均低于单化疗组,差异有统计学意义（P〈0．05）。康艾＋化疗组生存质量改善,卡氏评分（KPS评分）提高,改善率达到62．50％,2组比较差异有统计学意义（P〈0．05）。结论康艾注射液能提高多西他赛＋顺铂的近期疗效,减轻化疗的毒副反应,提高生存质量。