Capecitabine in advanced gastric cancer

Since the routine introduction of chemotherapy for advanced gastric cancer in the early 1990s, median survival for gastric cancer has improved from 3 months, with best supportive care alone, to > 11 months in recently reported Phase III trials of triplet chemotherapy. Capecitabine is an orally-active fluoropyrimidine, which is selectively metabolised to fluorouracil in tumour cells. The combinations of platinum compounds and capecitabine have been evaluated in two recent, large, Phase III trials demonstrating non-inferiority in efficacy compared with platinum plus continuous infusion fluorouracil. In view of the convenience and flexibility of patients in adjusting dosage when encountering toxicities, capecitabine is replacing continuous infusion fluorouracil as the backbone of combination chemotherapy in advanced gastric cancer patients. Future trials evaluating biologicals are now incorporating capecitabine combinations as control arms in both advanced disease and peri-operative settings in gastric cancer.     

Elderly patients with advanced colorectal cancer: which therapy is the safest?

Patients > 65 years of age are the fastest growing segment of the cancer population. It is estimated that within 20 years, > 75% of cases and 85% of deaths from colorectal cancer (CRC) will be in this setting. Concerns about cancer treatment in the elderly relate to comorbidities, which increase proportionally with age, physiological changes associated with ageing that may influence drug metabolism and toxicity, and diminishing life expectancy, which particularly impacts decisions surrounding the benefits of adjuvant therapies. Over the last 10 years, significant improvements in the treatment of advanced CRC with combination therapy have been made. The randomised trials that have defined these improvements did not exclude elderly patients; however, the median age of patients in these trials has generally been ～ 60 years. Thus, it appears that some degree of selection is involved with younger and presumably fitter patients being the subjects in most of the pivotal trials. The availability of new molecularly targeted agents and newly improved existing agents has expanded the range of treatment options available. This variety gives greater flexibility in dealing with different subsets of patients, such as the elderly. However, some fit elderly patients seem to tolerate combination therapy reasonably well, whereas studies on unfit elderly subjects are needed.     

E-cadherin在小肠腺癌、小肠腺瘤中的表达及其意义

目的探讨上皮性钙黏蛋白(E-cadherin)在小肠腺癌、小肠腺瘤及癌旁正常组织中的表达及其与小肠腺癌侵袭、转移的关系。方法应用免疫组化法观察42例小肠腺癌组织、16例小肠腺瘤组织及21例癌旁正常组织中E-cadherin蛋白的表达情况。结果 E-cadherin在小肠腺癌组织中的阳性表达率(38.1%)明显低于腺瘤组织(87.5%)和癌旁正常组织(90.4%)(P<0.01)。E-cadherin低表达与肿瘤分化程度、浸润深度及淋巴结转移有关(P<0.05),而与患者的性别、年龄及肿瘤大小、部位均无关(P>0.05)。结论 E-cadherin表达下调可能与小肠腺癌发生、发展有关,在小肠腺癌的恶性演进过程中具有重要意义,可作为新的生物学标志物。     

Emerging pharmacotherapeutic strategies for cholangiocarcinoma

Introduction: Although of limited clinical benefit, chemotherapy represents the cornerstone of management for patients with inoperable cholangiocarcinoma. The literature on chemotherapy in advanced cholangiocarcinoma is difficult to interpret because of the heterogeneity of cholangiocarcinoma, the use of various chemotherapeutic agents in different combinations and dosing regimens, and the small size of existing patient cohorts.

Areas covered: The authors discuss the major advances in the therapy of cholangiocarcinoma over the past decade. The audience will become familiarized with the contemporary medical management of cholangiocarcinoma and potentially useful agents/combinations for the therapy of this entity in the future.

Expert opinion: In recent years, gemcitabine-based chemotherapy has improved overall survival in advanced cholangiocarcinoma. Although gemcitabine–cisplatin combination represents the largely accepted standard for biliary cancers at present, very few studies so far have looked at the results in cholangiocarcinoma patients only. Therefore, large multicenter, randomized clinical trials are essential to identify the optimal treatment strategy for this rare tumor. In addition, regimens employing gemcitabine with oxaliplatin and/or fluoropyrimidines have shown promising results and warrant additional investigation in cholangiocarcinoma. The efficacy of a variety of newer agents is also now being tested in clinical trials.     

Pharmacogenetics of colorectal cancer

Colorectal cancer is one of the most common types of cancer in both men and women. Multiple chemotherapy combinations exist; however, there is currently no strategy for individualised therapy selection prior to treatment. Genetic polymorphisms in genes involved in the metabolism, transport or targets for the commonly used chemotherapy drugs (5-fluorouracil, irinotecan and oxaliplatin) have been described. Many require validation in large prospective trials before they can be used as markers for outcome and/or toxicity. This review describes the data available on polymorphisms in key genes that are associated with chemotherapy toxicity and response in colorectal cancer.     

XELOX方案与FOLFOX4方案治疗晚期结直肠癌75例

目的：比较奥沙利铂联合卡培他滨(XELOX)方案与奥沙利铂联合5-氟尿嘧啶/亚叶酸钙（5-FU/LV）(FOLFOX4)方案治疗晚期结直肠癌的近期疗效和毒副反应。方法：75例转移或复发晚期结直肠癌患者随机分为两组：奥沙利铂联合卡培他滨组(XELOX组,A组)37例,奥沙利铂联合5-FU/LV组(FOLFOX4组,B组)38例。A组给予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000mg[DK]?m-2,po,bid,d1~14;奥沙利铂130mg[DK]?m-2,静脉点滴,d1;1周期21d。B组给予5-FU,LV联合奥沙利铂方案化疗,奥沙利铂85mg[DK]?m-2,静脉点滴,d1;LV 200mg[DK]?m-2,静滴2h后予5-FU 400mg[DK]?m-2,推注,后续600mg[DK]?m-2持续静滴22h,d1,2;每2周重复1次,4周为1周期。两组患者均治疗2周期以上。按WHO标准评价客观疗效和毒副反应。结果：两组共75例患者均可评价疗效。A组：完全缓解（CR）3例,部分缓解（PR）15例,有效率(CR+PR)为48.6%;疾病进展时间(TTP)为6.12个月,生存时间(MST) 为13.7个月。B组：CR 3例,PR 16例,有效率为50.0%,TTP为5.91个月,MST为13.9个月。所有毒副反应都能耐受,A组消化道反应、血液学毒性、口腔炎、脱发的发生率显著低于B组(P<0.05);两组周围神经毒性和血小板减少发生率相近;A组的手足综合征发生率明显高于B组(P<0.05),但程度较轻,主要为Ⅰ~Ⅱ度。结论：XELOX方案与FOLFOX4方案的治疗晚期结直肠癌疗效相近,但XELOX方案具有用药更为方便,安全性更好等优点,值得临床一线使用。     

Which drug combination for colorectal cancer?

In Westernised countries, colorectal cancer (CRC) is second only to lung cancer as a cause of death from malignancy, with only 60% of patients alive at 5 years. In Stage II/III CRC, where the standard treatment is 5-fluorouracil (5-FU)/leucovorin, a recent clinical trial has shown that with the addition of oxaliplatin, fewer patients have relapsed or died at 40 months follow-up. The benefit was more pronounced in patients with Stage III than II CRC, and the addition of oxaliplatin to 5-FU/leucovorin should be considered in Stage III CRC. In metastatic CRC, where the standard treatment is 5-FU/leucovorin/irinotecan, a recent clinical trial has shown that the addition of bevacizumab, a mAb, to vascular endothelial growth factor, prolonged progression-free and overall survival. Bevacizumab is likely to become part of the standard therapy for metastatic CRC.     

顺铂联合5-氟尿嘧啶与奥沙利铂联合替吉奥一线治疗晚期胃癌的对比研究

目的比较顺铂(DDP)联合5-氟尿嘧啶(5-FU)与奥沙利铂(L-OHP)联合替吉奥(S-1)一线治疗晚期胃癌的有效性和安全性。方法回顾性分析该院2009年1月-2012年11月间收治的53例晚期胃癌患者,其中A组(DDP+5-FU,PF组)25例,具体为:DDP 20 mg·m-2静滴,第1～5天,5-FU 500 mg·m-2静滴维持24 h第1～5天,每4周重复。B组(L-OHP+S-1)28例,具体为:L-OHP 130 mg·m-2静滴2 h,第1天,S-1 40 mg·m-2早晚2次餐后服用,第1～14天,每3周重复。每2个周期评价疗效及毒性。结果 53例患者均可评价毒副反应和近期疗效,44例可评价远期疗效。A组中有效率和疾病控制率分别为44%和56%,B组中有效率和疾病控制率分别为53.6%和89.3%,两组差异均无统计学意义(P0.05)。A组中位疾病进展时间(TTP)和中位总生存时间(MST)分别为4.5个月和10.7个月,B组中位TTP和中位MST分别为8.0个月和13.0个月。两组中位TTP差异有统计学意义(P=0.032),中位MST差异无统计学意义(P=0.172)。两组毒副反应主要有血液学异常、肝肾功能异常、恶心呕吐、神经毒性等,以1～2级为主,可耐受,B组轻度神经毒性发生率明显高于A组,差异有统计学意义(P=0.012)。结论 S-1+L-OHP方案一线治疗晚期胃癌,同PF方案相比中位疾病进展时间延长,毒副反应均可耐受,给药方便,值得临床进一步研究。     

胶囊内镜对小肠疾病的诊断价值

目的探讨胶囊内镜对小肠疾病的诊断价值。方法对53例经胃、结肠镜检查未发现病因的腹痛及消化道出血患者应用OMOM胶囊内镜检查,对结果进行分析。结果 53例患者均完成对全小肠的观察,除1例未排出体外,其他胶囊均在2～6 d排出。共检出小肠病变39例(检出率73.58%),其中血管病变10例,结节型病变10例,炎症性病变8例,小肠溃疡6例,克罗恩病3例,淋巴管扩张1例,钩虫病1例。结论胶囊内镜对小肠疾病有较高的诊断价值,且安全性高,耐受性好。     

Systemic therapy for advanced pancreatic cancer: individualising cytotoxic therapy

Introduction: Pancreatic cancer is an aggressive solid tumour associated with a high risk of local invasion and metastatic spread. In the absence of validated screening approaches, many patients present with advanced, incurable disease. Despite advances in treatment, the prognosis for patients with advanced pancreatic cancer remains poor. The benefits of surgical resection and radiation are unproven in this setting and, as patients generally present with distant metastases, systemic therapy forms the mainstay of treatment. The importance of selecting the optimal cytotoxic therapy remains to be critical to improving outcome and retaining quality of life. This review sets out to compare the current therapies available for advanced pancreatic cancer.

Areas covered: This review examines the evolution of the systemic management of advanced pancreatic cancer, with a particular focus on the landmark Phase III trials identified from an extensive PubMed and Google scholar literature search. The article summarises the cytotoxic agents in use and the results of two decades of clinical trials to culminate in an almost doubling of survival in clinical trials.

Expert opinion: In the concluding expert opinion, the challenges interpreting and translating trial results into clinical practice are discussed, where patients are often older and of worse performance status. In the future, novel biomarkers might be used to tailor therapy.     

Effect of coefficient of viscosity and ambient temperature on the flow rate of drug solutions in infusion pumps

Context: FOLFOX6 and FOLFIRI regimens are often selected as the first- or second-line treatment for advanced or recurrent colorectal cancer. Patients are now able to undergo at-home treatment by using a portable disposable infusion pump (SUREFUSER^®A) for continuous intravenous infusion of 5-fluorouracil (5-FU). The duration of continuous 5-FU infusion is normally set at an average of 46?h, but large variations in the duration of infusion are observed.

Objective and methods: The relationship between the total volume of the drug solution in SUREFUSER^®A and the duration of infusion was analyzed by regression analysis. In addition, multiple regression analysis of the total volume of the drug solution, dummy variables for temperature, and duration of infusion was carried out.

Results: The duration of infusion was affected by the coefficient of viscosity of the drug solution and the ambient temperature.

Conclusion: The composition of the drug solutions and the ambient temperature must be considered to ensure correct duration of continuous infusion.     

胶囊内镜在不同小肠病变诊断中的应用价值

目的 探讨胶囊内镜在不同小肠病变诊断中的应用价值.方法 将128例接受胶囊内镜检查的患者按照临床表现分为A组(不明原因消化道出血)和B组(不明原因的腹痛、腹泻),分析其接受胶囊内镜检查的结果及临床意义.结果 胶囊内镜的总阳性检出率为36.00%(46/128),A组和B组的阳性率分别为58.62%(17/29)和29....     

口服泛影葡胺造影检查在粘连性小肠梗阻中的应用

目的：探讨口服泛影葡胺造影检查在粘连性小肠梗阻中的诊断及治疗价值。方法48例粘连性小肠梗阻患者口服76%泛影葡胺60~100 ml,行胃肠道造影检查,动态观察造影剂在胃肠道中的位置及通过情况,确定梗阻部位及梗阻的具体情况。结果38例患者造影剂在6~24 h后到达结肠,肠梗阻症状消失,另10例患者造影剂未到达结肠,症状、体征加重而行手术治疗,均获痊愈。结论口服泛影葡胺造影检查可以有效缩短肠梗阻缓解时间及住院时间,是治疗粘连性小肠梗阻的一种安全有效的方法,同时可以为早期手术提供线索。     

Second line treatment options for pancreatic cancer

Introduction: Patients with advanced pancreatic cancer (APC) refractory to first-line therapy have a dismal prognosis and limited therapeutic options, with only one option consisting of nanoliposomal irinotecan in combination with fluorouracil and folinic acid which was approved by FDA based upon results of the phase III NAPOLI-1 study.

Areas covered: We performed a literature search for relevant published clinical trials, abstracts of trials in progress and ongoing or planned trials for the second line treatment of APC using Pubmed.com, ClinicalTrials.gov and American Society of Clinical Oncology (ASCO) abstract search as sources. We present an in-depth analysis of the phase I-III clinical trials determining the role and efficacy of second-line treatment in patients with APC. We also describe ongoing studies and rationale for future investigation.

Expert opinion: Despite advances in first-line therapy such as gemcitabine/nab-paclitaxel and FOLFIRINOX in APC, median overall survival remains less than 12 months, highlighting the need to develop second-line therapies. In order to establish much needed effective second-line treatment options, we need cooperative efforts among institutions and community practices in enrolling these refractory patients in clinical trials. It should be emphasized that in addition to chemotherapy options, all patients should have the opportunity to consult with nutritionist, social worker and palliative care health providers to assist with goals of care, symptom management and end of life discussions.     

老年患者术后炎性肠梗阻的诊治体会

目的:探讨老年患者术后炎性肠梗阻的特点、诊断和治疗方案.方法:回顾性分析24例术后炎性肠梗阻的临床资料和治疗结果.结果:23例经禁食、胃肠减压、营养支持等保守治疗痊愈,1例手术治疗后治愈,无死亡病例.结论:术后早期炎性肠梗阻一般发生在腹部手术后2周左右,有典型肠梗阻表现,首选保守治疗,手术应谨慎.     

腹腔镜辅助用于小肠肿瘤切除术的临床价值

目的探讨腹腔镜辅助小肠肿瘤切除术的临床应用价值。方法 43例小肠肿瘤患者随机分为腹腔镜辅助手术组(n=20)和开放手术组(n=23),比较两组的切口长度、手术时间、术中失血量、止痛药物需求、术后饮食恢复时间、术后住院日、术后并发症。结果两组患者基线资料差异无统计学意义(P>0.05)。腹腔镜辅助手术组在切口长度、术中失血量、术后疼痛及术后恢复流质饮食时间方面,比开放手术有优势(P<0.05)。结论腹腔镜辅助小肠肿瘤切除术安全可行,具有创伤小、恢复快的优点。     

Advances in pharmacotherapy of small cell lung cancer

Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastatic dissemination and responsiveness to initial therapy. The incidence of SCLC has been declining over the past two decades. Limited-stage SCLC is a potentially curable disease with long-term survival of ～ 20% when treated with platinum-based chemotherapy plus concurrent thoracic radiation and prophylactic cranial irradiation. For patients with extensive-stage SCLC, survival can be increased with combination platinum-based chemotherapy, but the disease remains incurable.

Areas covered: This review looks at the current advances in pharmacotherapy for SCLC.

Expert opinion: Many chemotherapeutic strategies and newer cytotoxic agents have been evaluated in SCLC, and some had promising activity in early clinical trials. However, none have demonstrated consistent improvements in outcome over standard platinum-based treatment. Similarly, although many potential molecular targets have been identified in preclinical studies of SCLC, molecularly targeted therapy has yet to demonstrate any substantial activity in clinical trials. Nonetheless, future advances in this disease will undoubtedly depend on improvements in our understanding of the molecular mechanisms that drive the proliferation and survival of SCLC cells.     

术后早期炎性肠梗阻的诊治分析

目的 探讨腹部手术后早期炎性肠梗阻的病因、临床特点和诊治原则.方法 回顾性分析我院近期诊治的术后早期炎性肠梗阻19例.结果 17例患者经胃肠减压、抗炎、应用生长抑素、全胃肠外营养结合中药等保守治疗治愈;2例患者经手术治疗,无效后经保守治疗治愈.平均治愈时间为12d,无1例肠坏死.结论 术后早期炎性肠梗阻好发于腹部手术后2周以内,主要是因为腹腔内炎症所致广泛黏连所引起;症状以腹胀为主,腹痛相对较轻,部分患者有少量肛门排气排便,体征虽典型,但很少发生肠绞窄坏死.治疗上最好先予以生长押素为主的保守治疗,治疗过程中应严密现察,如出现肠坏死、腹膜炎征象时应及时中转手术.     

Small molecule dipeptidylpeptidase IV inhibitors under investigation for diabetes mellitus therapy

Importance of the field: Fluoropyrimidines with oxaliplatin or irinotecan, bevacizumab, cetuximab and panitumumab constitute the drugs currently approved by the FDA for the treatment of patients with metastatic colorectal cancer (mCRC). Patients who have progressed on the approved drugs pose a major challenge for medical oncologists, as the therapeutic choices outside the context of a clinical trial are limited.

Areas covered in this review: Mitomycin C is an old drug that acts synergistically with capecitabine and irinotecan. Relevant studies were identified in PubMed (years 1950 – 2009), Ovid, Cochrane database and the American Society of Clinical Oncology abstracts (years 1995 – 2009) using the following search terms: mitomycin C, fluorouracil, capecitabine, irinotecan, oxaliplatin, and colorectal cancer. Only studies using the combination of mitomycin C with one of the aforementioned agents were selected.

What the reader will gain: An overview of the clinical trials where mitomycin has been used in combination with modern compounds in the various settings of metastatic colorectal cancer.

Take home message: Mitomycin C combinations are less efficacious than modern drugs in the first-line treatment of colorectal cancer. However, they are acceptable alternatives for best supportive care in colorectal cancer that is refractory to standard regimens, as they show some modest efficacy at low cost.     

长春瑞滨联合顺铂、亚叶酸钙/5-氟脲嘧啶治疗晚期食管癌21例

目的探讨长春瑞滨(NVB)联合顺铂(DDP)、亚叶酸钙(CF)、5-氟尿嘧啶(5-Fu)的NFP方案治疗晚期食管癌的近期疗效与不良反应。方法NVB 25 mg.m-2,静脉注入,d1,8;DDP 30 mg.m-2,静滴,d1~3;CF 200 mg,静滴,d1~5;5-Fu 500 mg.m-2,静滴8 h;28 d为一周期,两周期后评价疗效。结果可评价疗效的21例中完全缓解(CR)1例(4.8%),部分缓解(PR)7例(33.3%),总有效率(CR PR)38.1%(8/21)。主要不良反应静脉炎、骨髓抑制和胃肠道反应,经对症处理患者均能忍受。结论长春瑞滨联合顺铂、亚叶酸钙/5-氟脲嘧啶治疗晚期食管癌疗效较好,毒副反应可以耐受,值得进一步扩大临床研究及应用。