转移性结直肠癌维持治疗的进展

摘 要：目前,转移性结直肠癌（metastatic colorectal cancer,mCRC）的标准一线治疗方案是在化疗药物基础上联合分子靶向药物。对于完成一线治疗且达到完全缓解、部分缓解或稳定的转移性结直肠癌患者,与持续化疗或单纯观察相比,维持治疗不仅可以巩固一线治疗疗效,延缓疾病进展,而且可以减轻化疗药物的蓄积性不良反应,改善患者生存质量,最终达到延长总生存期的目的。维持治疗包括化疗药物、分子靶向药物和化疗药物联合分子靶向药物维持治疗3种方式,近年来已成为转移性结直肠癌研究的重要方向,但仍有许多问题尚待进一步探索和研究。     

交替化疗方案治疗转移性结直肠癌

以氟尿嘧啶、奥沙利铂、伊立替康为基础的化疗是转移性结直肠癌的主要治疗方法.近年来许多研究探讨了这些不同活性药物之间的联合应用,并进行了多种联合治疗模式的尝试.多项临床试验表明,交替方案化疗有效率高且毒性较低,为转移性结直肠癌的联合化疗拓展了新的领域.     

结直肠癌术后患者采用改良FOLFOX6方案治疗的疗效观察

目的探讨结直肠癌术后患者采用改良FOLFOX6(mFOLFOX6)方案治疗的近期疗效。方法将62例结直肠癌术后患者随机分为采用mFOLFOX6方案治疗的观察组(31例)和采用FOLFOX6方案治疗的对照组(31例),对比分析两组患者的近期疗效和不良反应。结果采用mFOLFOX6方案治疗的观察组患者的胃肠道反应、骨髓毒性、神经毒性等不良反应及在生活质量评分方面均优于对照组,差异有统计学意义(P<0.05);近期疗效与采用FOLFOX6方案治疗的对照组相似。结论 mFOLFOX6方案应用于结直肠癌术后患者不良反应较轻,患者生活质量较高,近期疗效确定。     

不可切除转移性结直肠癌的治疗策略

 化疗或联合分子靶向治疗仍是不能手术切除转移性结直肠癌的主要手段。对于一线治疗后获得疾病控制的患者,间歇治疗和维持治疗等新策略的疗效可能不劣于持续给药至疾病进展或不能接受毒性为止的传统策略,而且可以减少药物相关不良反应和提高生活质量。     

两种化疗方案治疗结直肠癌术后放疗后复发患者的临床观察

目的观察L-OHP+5-Fu+CF与5-Fu+CF两种化疗方案的疗效和毒副反应,及患者对两种方案的接受程度。方法将53例患者分为两组,L-OHP+5-Fu+CF治疗组(简称A组)29例,5-Fu+CF治疗组(简称B组)24例。结果治疗后两组均未出现完全缓解病例。A组PR 7例,有效率24.1%;B组PR 5例,有效率20.8%。A组化疗后患者自觉症状缓解率为82.8%(24/29),B组62.5%(15/24)。A组患者对化疗的接受率为35.9%(11/29),B组75.0%(18/24)。A组1,2,3年生存率分别为86.2%、48.3%和31.0%,B组分别为83.3%、41.7%和25.0%。毒副反应B组高于A组,以末梢神经毒性,白细胞、红细胞下降及恶心、呕吐为主,程度多为Ⅰ、Ⅱ级,多数患者可耐受。结论两组化疗方案相比较,在疗效方面,L-OHP+5-Fu+CF方案并未优于5-Fu+CF方案,但L-OHP+5-Fu+CF组毒副反应高于5-Fu+CF组,两组均可耐受。     

转移性结直肠癌西妥昔单抗治疗的疗效及安全性

[目的]观察西妥昔单抗对K-ras野生型转移性结直肠癌的疗效和不良反应。[方法]对34例接受西妥昔单抗单药(1例)或联合化疗(33例)治疗的K-ras野生型转移性结直肠癌患者进行疗效及不良反应分析。[结果]34例患者均可评价疗效及不良反应。全组有效率41.2%,中位无进展生存时间6.5个月,中位生存时间16.9个月。7例一线治疗患者有效率57.1%,中位无进展生存时间7.2个月,中位生存时间21.4个月。21例二线治疗患者,有效率38.1%,中位无进展生存时间6.9个月,中位生存时间15.7个月。6例三线或三线以上患者,有效率33.3%。最常见的不良反应为皮肤毒性,其次骨髓抑制,大多为Ⅰ～Ⅱ度。[结论]国人K-ras野生型转移性结直肠癌患者中,西妥昔单抗联合化疗在一线、二线及多线治疗中均获得较好的客观缓解及疾病控制,同时不良反应可耐受。     

结直肠癌化学治疗临床研究进展

氟尿嘧啶联合醛氢叶酸钙(FL方案)已成为结直肠癌的标准治疗方案，且以FL静脉持续滴注方案为优；口服氟尿嘧啶类药物在生存率上至少与已确立的FL方案相当，而毒副反应方面则更优越；奥沙利铂(L-OHP)与FL联合使用在高危结直肠癌治疗中显示出比标准FL方案有生存上的优势，3年无瘤生存率更高。分子靶向药物和有效抗肿瘤细胞毒药物的联合序贯应用进一步延长转移性结直肠癌患者的生存期，但最佳给药顺序仍有争论。     

替吉奥胶囊单药治疗化疗失败的转移性结直肠癌

目的探讨替吉奥胶囊（S-1）治疗晚期结直肠癌的临床疗效和安全性。方法 7例患者接受替吉奥胶囊化疗,观察近期疗效及患者不良反应。结果 7例患者中3例部分缓解（PR）,4例病情稳定（SD）,不良反应主要为中性粒细胞减少,多为Ⅰ度,7例患者均完成治疗,未发生与治疗相关性死亡。结论 S-1治疗晚期结直肠癌疗效较好、不良反应轻微,有可能成为化疗失败的转移性结直肠癌患者的补救措施。     

贝伐珠单抗联合化疗治疗转移性结直肠癌的研究进展

结直肠癌目前常规化疗方案为FOLFOX方案(氟尿嘧啶、亚叶酸钙、奥沙利铂),大量临床试验证明贝伐珠单抗联合FOLFOX方案治疗恶性肿瘤安全有效,但有高血压、神经毒性、胃肠道出血和穿孔等不良反应产生.对转移性结直肠癌患者应用此联合方案对整体生存时间、肿瘤应答率和生存质量进行的研究得出了不同的结论,其安全性和有效性仍需大样本随机对照试验或Meta分析来进一步研究证明.     

The role of maintenance therapy in metastatic colorectal cancer

During the last decade, numerous new agents were introduced into the therapy of metastatic colorectal cancer. Treatment duration and maintenance therapy, however, still remain a controversial issue. More and more results from clinical trials become available that assess the role of maintenance chemotherapy in combination with the angiogenesis inhibitor bevacizumab and epidermal growth factor inhibitors. Taken together, these data suggest that some form of maintenance therapy leads to a better patient outcome and is thus appropriate. Our challenge remains the need to identify and predict the required therapeutic intensity whether by biomarkers or clinical parameters. As also side effects may increase due to drug combinations, quality of life issues need to be carefully considered for each individual patient.     

转移性结直肠癌维持治疗研究进展

结直肠癌是最常见的恶性肿瘤之一。近年来,奥沙利铂、5-FU类制剂、伊立替康、VEGF抗体、EGFR抑制剂等药物的使用延长了晚期结直肠癌患者的5年生存率,显著改善患者的生活质量。维持治疗是指对一线治疗后获益的患者,停用某些毒副反应较大的药物,保留低毒性药物继续治疗的一种治疗模式。因此,一些临床研究评估了上述药物在转移性结直肠癌患者一线治疗获益后的维持治疗的疗效及安全性。本文就转移性结直肠癌维持治疗方案的临床研究作一综述,全面地了解转移性结直肠癌维持治疗的相关进展。     

转移性结直肠癌维持治疗的研究现状与治疗策略

结直肠癌是常见的恶性肿瘤之一,其发病率和死亡率分别位于第三位和第四位。大约60%的患者确诊时已处于晚期,其5年生存率在13%左右。近20年来,由于转移性结直肠癌(mCRC)晚期一线化疗方案及靶向药物的规范化应用,mCRC的治疗获得了重大突破。奥沙利铂、卡培他滨、贝伐珠单抗、西妥昔单抗等药物的应用使患者的中位生存期提高了一倍,5年生存率提高了20%。mCRC晚期一线治疗的常规模式是持续用药,直至病情进展或出现不可耐受的毒性。但是由于化疗药物的毒性累积,只有三分之一的患者能够坚持接受治疗直至病情进展。而患者在完成既定的初始化疗周期数,达到CR/PR/SD后,继续采用低剂量、低毒性的药物进行维持治疗,既可以延缓肿瘤的进展和转移,又可以减轻药物的毒副作用。目前,维持治疗已经成为mCRC晚期一线化疗后的主要治疗模式。但是,mCRC的最佳维持治疗方案仍无定论,现有的维持治疗方案仍不能找到最佳疗效与最大生活质量之间的平衡点。本文将回顾mCRC现有的维持治疗方案的临床研究,总结mCRC维持治疗现状,并对个体化的治疗策略进行讨论。     

Capecitabine maintenance therapy after first-line chemotherapy in patients with metastatic colorectal cancer

Objective  

To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer (mCRC) patients.     

含卡培他滨联合化疗方案序贯卡培他滨维持治疗转移性乳腺癌患者的疗效观察

目的探讨含卡培他滨联合化疗方案治疗晚期转移性乳腺癌(MBC)后继续予卡培他滨单药维持治疗的疗效和安全性。方法选取2012年6月至2016年6月间湖南省肿瘤医院收治的158例MBC患者,分别接受3种不同的含卡培他滨联合化疗方案治疗后,将疗效评价为缓解或稳定的139例患者分为维持治疗组(73例)和未维持组(66例)。维持治疗组患者予以口服卡培他滨单药维持治疗,未维持组患者予以定期随访观察。评价所有患者的疗效和不良反应。结果维持治疗组患者中位无进展生存时间(PFS)明显长于未维持组患者,差异有统计学意义(P<0.05)。158例患者联合治疗近期客观有效率(ORR)为48.1%,疾病控制率(DCR)为88.0%。年龄>45岁的患者有较高的ORR(P<0.05)。维持治疗组患者维持阶段ORR为16.4%,DCR为68.5%。在亚组分析中,联合化疗采用GX方案的患者中位PFS较TX或NX联合化疗有延长的趋势,转移灶≥3处患者的中位PFS较转移灶数目为1~2处有缩短的趋势,转移后2线及以上治疗患者的中位PFS较转移后1线治疗的患者也有缩短的趋势,但差异均无统计学意义(均P>0.05)。主要不良反应为血液学不良反应、手足综合征和胃肠道不良反应,患者均可以耐受。结论卡培他滨是MBC维持治疗的有效药物,能够延缓患者的疾病进展,且具有较轻的不良反应。     

Liver-directed therapy in metastatic colorectal cancer

Introduction: Colorectal cancer is a significant global health issue with over 1 million cases diagnosed annually throughout the world. 15% of patients diagnosed with colorectal cancer will have liver metastases and 60% will develop liver metastases if they have metastatic disease. Oligometastatic colorectal cancer confined to the liver represents an intermediate state in the evolution of metastatic capacity that opens the opportunity for local interventions.

Areas covered: The literature supports long-term survival if patients undergo liver resection of colorectal metastases. This article reviews the liver-directed therapeutic strategies available for the management of metastatic liver disease including hepatic arterial infusion therapy, radiofrequency ablation, radiation therapy and transarterial chemoembolization.

Expert commentary: Great advances have been made with the use of liver directed therapies. In the USA using hepatic arterial infusions with FUDR and Decadron along with systemic therapy, 5 year survivals after liver resection have improved. In Europe with the use of HAI of Oxaliplatin, more patients have been able to get to resection and have obtained higher survival rates, even in second line therapy. New advances in ablative therapy have improved results to get all disease treated at resection for the treatment of reccurrence     

Third-line therapy for metastatic colorectal cancer

Background The past years’ therapy for colorectal cancer has evolved rapidly with the introduction of novel cytotoxic agents such as irinotecan, capecitabine and oxaliplatin. Further advances have been achieved with the integration of targeted agents such as bevacizumab, cetuximab and recently, panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). Materials and methods We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data on median overall survival (mOS), median time to progression (mTTP) and response rate were recorded. Results We found 27 articles and 22 abstracts to fulfil the criteria. Patients who received regimens containing oxaliplatin and infusional 5-fluorouracil (5-FU) demonstrated mTTP up to 7 months and a mOS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. Conclusion Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted in the future.     

Targeted therapy for metastatic colorectal cancer

Introduction: Outcomes in metastatic colorectal cancer are improving, with better understanding and use of targeted therapies.

Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of systemic treatment of metastatic colorectal cancer. This article reviews the current evidence for targeted therapies in advanced colorectal cancer, including up-to-date data regarding anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF) agents, the relevance of primary tumor location and novel subgroups such as BRAF mutated, HER2 amplified, and mismatch-repair-deficient cancers.

Expert commentary: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for metastatic colorectal cancer (mCRC). The use of EGFR-targeted antibodies should be restricted to patients with extended RAS wild-type profiles, and there is evidence that they should be further restricted to patients with left-sided tumors. Clinically, mCRC can be divided into subgroups based on RAS, BRAF, HER2, and MMR status, each of which have distinct treatment pathways.     

Efficacy of third-line therapy using bevacizumab in a patient with metastatic colorectal cancer

Bevacizumab is currently approved in association with first- and second-line 5-fluorouracil–based chemotherapy regimens for patients with metastatic colorectal cancer. Few data about the usefulness of bevacizumab in third-line settings are available. We describe a patient refractory to folfiri and folfox chemotherapy regimens who showed a dramatic and durable response to bevacizumab and folfiri. We also review and discuss the available literature.     

Efficacy of capecitabine-based combination therapy and single-agent capecitabine maintenance therapy in patients with metastatic breast cancer

Objective

The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer (MBC).

Patients and methods

A total of 98 MBC patients were treated with capecitabine combined with vinorelbine (NX).

Results

The median number of treatment was 6 cycles (1-7 cycles). There were two cases of complete remission (CR), 58 partial remission, 27 stable disease (SD), 11 progression disease. The overall response rate (ORR) (CR + PR) was 61.2%. The clinical benefit rate (CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR (CR + PR) was 4%. The CBR was 48%. The median progression-free survival (PFS) was 12 months. In maintenance therapy or not, the median post metastasis survival rate (MSR) was 63 and 28 months, respectively. In the combination therapy group, the major grade 3/4 toxicities included hand-foot syndrome (3.1%), skin pigmentation (2.0%), diarrhoea and abdominal distension (5.1%), stomatitis (1.0%), and leukopenia (20.4%).

Conclusions

Capecitabine-based combination therapy and single-agent capecitabine maintenance therapy were well tolerated and effective to MBC.