Adjuvant systemic chemotherapy with gemcitabine for stage IV pancreatic cancer: a preliminary report of initial experience

BACKGROUND: The effects of gemcitabine on postoperative adjuvant chemotherapy were evaluated in patients with stage IV pancreatic cancer. The results were compared with those of our historical control patients treated with surgery alone. PATIENTS AND METHODS: Nineteen patients with stage IV pancreatic cancer who had pancreatic resection with curative intent during the 5 years up to February 2003 were enrolled in this study. Nine cases received postoperative adjuvant chemotherapy with biweekly administration of 1,000 mg/m(2) gemcitabine, while the remaining 10 cases underwent surgery without any adjuvant chemotherapy. Results: The chemotherapy was well tolerated with only mild symptomatic and hematologic toxicities. The disease-specific cumulative survival rates of the chemotherapy and surgery-alone groups were 86 and 70% at 1 year, and 50 and 12% at 2 years, with a median survival of 20 and 14 months, respectively (p = 0.0255). The disease-free interval was improved, and the occurrence of hepatic metastasis was reduced in the chemotherapy group compared with the surgery-alone group. CONCLUSIONS: Adjuvant systemic chemotherapy utilizing gemcitabine was feasible with acceptable adverse effects, and showed some survival benefit in stage IV pancreatic cancer patients. Further investigation into gemcitabine-based combination therapies is warranted.     

Neoadjuvant Chemotherapy in breast cancer

Neoadjuvant chemotherapy for breast cancer was originally used in locally advanced inoperable disease in order to achieve surgical resection. It was then extended to operable breast cancer with a view to downstaging tumors to facilitate breast-conserving surgery. Long-term results from randomized studies have shown no difference in disease-free or overall survival between neoadjuvant and adjuvant chemotherapy. The main benefit of neoadjuvant chemotherapy is its ability to downstage large tumors with a view to treatment by breast-conserving surgery. Since pathological complete response is thought to be main factor to achieve long-term survival, development of new agent or novel combination treatment is needed.     

胆道系统肿瘤的药物治疗

手术切除是目前胆道系统肿瘤唯一的根治方法,但早期手术切除后复发率高,且患者诊断时大多为中晚期,已失去手术机会,预后较差。荟萃分析认为,术后辅助治疗能改善患者预后,BILCAP研究中卡培他滨辅助化疗虽未在意向治疗患者中达到研究终点,但在协定治疗患者中显示存在生存获益。吉西他滨联合顺铂(GC方案)仍是晚期一线标准化疗方案,吉西他滨联合替吉奥(GS方案)和吉西他滨、替吉奥联合顺铂(GCS方案)亦是一线治疗可选择的方案。IDH1、FGFR2作为肝内胆管癌的两种主要驱动基因已成为靶向治疗的研究热点,免疫检查点抑制剂单药或联合治疗研究亦逐步开展。本文旨在回顾胆道系统肿瘤的药物治疗进程,展望其治疗前景。     

The evolving role of endocrine therapy for breast cancer

The indirect comparison of LHRH agonist with tamoxifen showed similar efficacy in the adjuvant treatment of premenopausal endocrine-responsive breast cancer patients. Furthermore, LHRH agonist is as effective as cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy. Data concerning combination of LHRH agonist with third-generation aromatase inhibitors are still lacking. Moreover, duration of therapy with LHRH agonist is still a matter of debate. In randomized clinical trials, each of the third-generation aromatase inhibitors (AIs) has demonstrated efficacy in the adjuvant treatment of postmenopausal women with receptor' -positive tumors. Anastrozole has been shown to improve disease-free survival when compared with tamoxifen, letrozole has been shown to further reduce the rate of breast cancer events when given as extended adjuvant therapy in women completing between 4.5 and 6 years of tamoxifen, and exemestane has been shown to improve disease-free survival when substituted for tamoxifen after an initial 2-3 years of adjuvant therapy. Although long-term follow-up for safety and overall survival continues in each of these trials, currently available data suggest that an AI should now be included as part of adjuvant endocrine therapy for the great majority of receptor-positive postmenopausal patients.     

Systemic therapy of hepatocellular carcinoma: Are we making progress?

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer deaths. Surgical resection, with or without transplantation, can result in long-term survival. However, surgery can only be performed in about 15% of patients with HCC and the 5-year survival rate is only approximately 33%–50% after potentially curative resection. Percutaneous ethanol injection, radiofrequency ablation, and transarterial chemoembolization are invasive techniques that have shown efficacy in reducing tumor bulk. Similarly, systemic chemotherapy may induce tumor responses, but a survival benefit has not been clearly demonstrated. In addition, the lack of efficacy of antiandrogens, tamoxifen, and single-agent interferon has now been confirmed. Sorafenib is a multikinase inhibitor with antiangiogenic, proapoptotic, and Raf kinase inhibitory activity. In a large, multicenter, randomized, phase 3 trial there was a significant improvement in both time to disease progression and overall survival with sorafenib compared with placebo. Sorafenib is the first agent to demonstrate a consistent improvement in overall survival for patients with advanced HCC. Further studies are required to determine the role of other molecular-targeted therapies, either alone or in combination with sorafenib in patients with advanced HCC. Further studies are also required to determine the role of sorafenib in combination with locoregional therapies (eg, transarterial chemoembolization), and the role of sorafenib as adjuvant therapy following surgery.     

Survival Comparisons for Breast Conserving Surgery and Mastectomy Revisited: Community Experience and the Role of Radiation Therapy

ObjectivesEvidence suggests superiority of breast conserving surgery (BCS) plus radiation over mastectomy alone for treatment of early stage breast cancer. Whether the superiority of BCS plus radiation is related to the surgical approach itself or to the addition of adjuvant radiation therapy following BCS remains unclear.ResultsData from 5335 women were included, of which two-thirds had BCS and one-third had mastectomy. Surgical decision trends changed over time with more women undergoing mastectomy in recent years. Women who underwent BCS versus mastectomy differed significantly regarding age, cancer stage/grade, adjuvant radiation, chemotherapy, and endocrine treatment. Overall survival was similar for BCS and mastectomy. When BCS plus radiation was compared to mastectomy alone, 3-, 5-, and 10-year overall survival was 96.5% vs 93.4%, 92.9% vs 88.3% and 80.9% vs 67.2%, respectively.ConclusionThese analyses suggest that survival benefit is not related only to the surgery itself, but that the prognostic advantage of BCS plus radiation over mastectomy may also be related to the addition of adjuvant radiation therapy. This conclusion requires prospective confirmation in randomized trials.     

G17DT: an antigastrin immunogen for the treatment of gastrointestinal malignancy

G17DT (Gastrimmune) is an antigastrin-17 immunogen, raising antibodies that blockade gastrin-stimulated tumor growth. It has completed Phase III trials in patients with pancreatic cancer, and Phase III trials in gastric cancer are planned. Preclinical studies have confirmed that the G17DT-induced antibodies both reduce gastrin-17-stimulated gastric acid secretion and inhibit gastrin from interacting with the cholecystokinin-2 receptor. The efficacy of both passive and active immunization with G17DT has been established in a number of tumor systems, with additive effects demonstrated in combination chemotherapy in pancreatic, colon and gastric tumor models. Phase I/II studies in advanced gastrointestinal malignancies have shown no systemic or autoimmune reactions to active immunization with G17DT. The use of an optimized dose and dosing schedule has yielded a high proportion of antibody responders (70%), with minimal side effects and antibody titers measurable within 2 - 4 weeks. Phase II trials of G17DT in combination with chemotherapy have also been conducted in gastric and colorectal cancer. A Phase III, multicenter, double-blind, randomized, controlled trial of G17DT versus placebo in patients with advanced pancreatic cancer confirmed improved survival of patients in the G17DT group through an intention-to-treat analysis. The results of a randomized, double-blind, multinational, multicenter study of G17DT in combination with gemcitabine versus placebo and gemcitabine in patients with advanced pancreatic cancer failed to show improved overall survival except on subset analysis of patients with high antibody titers. Therefore, G17DT represents an emerging new modality for gastrointestinal malignancy.     

Capecitabine: a new adjuvant option for colorectal cancer

Colorectal cancer continues to pose a major public health threat in the United States. Without postsurgical adjuvant therapy, approximately 50% of patients will have recurrent disease and die within five years. Since 1990, five new chemotherapy agents have been added to the therapeutic armamentarium for management of colorectal cancer, and agents traditionally used to treat metastatic and advanced disease increasingly are being applied in the adjuvant setting. One such treatment, capecitabine, offers patients the benefit of oral dosing and permits at-home self-management. A phase III randomized trial, Xeloda in Adjuvant Colorectal Cancer Treatment, demonstrated that treatment with single-agent capecitabine was equivalent to bolus 5-fluorouracil with leucovorin with respect to disease-free survival and overall survival, with significantly less diarrhea, stomatitis, neutropenia, nausea and vomiting, and alopecia. This article reviews the findings and discusses how oncology nurses can help provide effective education and monitoring for patients using oral treatment in the adjuvant setting.     

吉西他滨联合卡培他滨在转移性胰腺癌一线化疗中的疗效及安全性分析

目的分析研究吉西他滨联合卡培他滨在转移性胰腺癌一线化疗中的疗效及安全性。方法 23例初治转移性胰腺癌一线化疗接受吉西他滨联合卡培他滨:吉西他滨1000 mg/m2,静脉滴注30 min,第1、8天;卡培他滨650 mg/m2,2次/天,口服,第1~14天;每3周1个疗程,评价它的总生存、无进展生存、客观缓解率、临床获益率、临床获益反应、糖类抗原19-9(CA19-9)缓解率和不良反应等。结果 23例转移性胰腺癌患者中,4例出现部分缓解,6例获得疾病稳定,13例出现按肿瘤进展,总客观缓解率为17.4%,平均缓解持续时间为6.8个月,临床获益为43.5%,临床获益反应率为52.2%,CA19-9缓解率为65.2%,中位无进展生存为6.1个月,1年无进展生存率14.2%;中位生存时间为7.3个月,1年生存率为25.1%。绝大部分治疗相关不良反应是1至2级,最常见的3/4毒性反应为中性粒细胞减少。结论研究证实吉西他滨与卡培他滨联合方案可成为转移性胰腺癌一线化疗方案之一;同时,临床获益反应在疗效相近的化疗方案的选择上有着重要的指导作用。     

Her signaling in pancreatic cancer

Pancreatic cancer remains a treatment-refractory cancer. Standard therapy for metastatic cancer is gemcitabine chemotherapy, with a median survival of 5-6 months. The epidermal growth factor receptor (EGFR) is commonly expressed in pancreatic cancer and has been evaluated as a therapeutic target. A Phase III trial of gemcitabine with or without the EGFR inhibitor, erlotinib, demonstrated a modest but significant prolongation of survival with the addition of erlotinib. A Phase II trial of gemcitabine with the anti-EGFR antibody cetuximab resulted in a 1-year survival of 32%. A Phase III trial of gemcitabine with or without cetuximab and a randomized Phase II trial of the Murren regimen with or without cetuximab are completed; results for both are anticipated in 2007. A Phase I trial of gemcitabine with the EGFR/Her-2 inhibitor, lapatinib, is completed. Improved patient selection and rational combination of targeted therapies will be necessary to optimize the management of patients with this tragic disease.     

Her signaling in pancreatic cancer

Pancreatic cancer remains a treatment-refractory cancer. Standard therapy for metastatic cancer is gemcitabine chemotherapy, with a median survival of5 – 6 months. The epidermal growth factor receptor (EGFR) is commonly expressed in pancreatic cancer and has been evaluated as a therapeutic target. A Phase III trial of gemcitabine with or without the EGFR inhibitor, erlotinib, demonstrated a modest but significant prolongation of survival with the addition of erlotinib. A Phase II trial of gemcitabine with the anti-EGFR antibody cetuximab resulted in a 1-year survival of 32%. A Phase III trial of gemcitabine with or without cetuximab and a randomized Phase II trial of the Murren regimen with or without cetuximab are completed; results for both are anticipated in 2007. A Phase I trial of gemcitabine with the EGFR/Her-2 inhibitor, lapatinib, is completed. Improved patient selection and rational combination of targeted therapies will be necessary to optimize the management of patients with this tragic disease.     

Trastuzumab for gastric cancer

Background: Gastric cancer is a disease with different management approaches in different regions, especially between Western and Asian countries. Surgery is the mainstay of treatment for non-metastatic disease. Perioperative chemotherapy or adjuvant radio-chemotherapy is recommended, since recurrences are common after curative resection. Unfortunately, advanced or metastatic gastric cancer constitutes the majority of patients in clinical practice. For these patients systemic chemotherapy is the standard treatment, to provide palliation and prolong survival; however, prognosis remains poor. Several molecular targeting agents are under evaluation in international randomized studies. Objective: To review chemotherapy and targeted therapies for gastric cancer, chemical and pharmacological characteristics of trastuzumab, and evidence for its clinical use in gastric cancer. Methods: Examination of relevant literature. Results/conclusions: HER-2 is overexpressed/amplified in approximately 22% of gastric cancer patients. Trastuzumab, a recombinant humanized anti-HER-2 monoclonal antibody, is, to our knowledge, the first biological therapy that has showed a survival improvement by nearly 3 months (reduced risk of death by 26%), thus trastuzumab in combination with chemotherapy is a treatment option for patients with HER2-positive advanced gastric cancer. Trastuzumab's role in curative gastric cancer treatment needs to be studied, as well as monotherapy, maintenance therapy and second line treatment in the palliative setting.     

胰腺癌根治术后辅助化疗对患者生存情况影响的Meta分析

目的系统评价胰腺癌根治术后辅助化疗对胰腺癌根治术患者生存率的影响。方法计算机检索h e Cochrane Library（2013年第11期）、Pub Med、EMbase、CBM、CNKI、VIP和Wan Fang Data数据库,查找有关胰腺癌根治术后辅助化疗对胰腺癌根治术患者生存情况影响的随机对照试验（RCT）,检索时限均为建库至2013年11月。由2位评价者按照纳入与排除标准独立筛选文献、提取资料并评价纳入研究的方法学质量后,采用Rev Man5.2软件进行Meta分析。结果共纳入7个RCT,包括1 079例患者,其中试验组544例,对照组535例。Meta分析结果显示,胰腺癌根治术后辅助化疗较单纯根治术能延长患者的总生存时间[WMD=5.45,95%CI（2.52,8.39）,P=0.000 3],提高2年生存率[RR=1.17,95%CI（1.01,1.35）,P=0.03]和5年生存率[RR=1.80,95%CI（1.24,2.62）,P=0.002],其差异均有统计学意义。但两组在1年生存率方面差异无统计学意义[RR=1.02,95%CI（0.94,1.11）,P=0.65]。结论现有证据表明,胰腺癌根治术后应接受术后辅助化疗。     

Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past, the present and the future

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.     

Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past,the present and the future

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.     

如何提高胰腺癌的手术切除率

目前胰腺癌的总体5年生存率仍徘徊在5%左右,但是近年来随着外科手术和放化疗技术的进步,胰腺癌的治疗模式已有明显的改善。对于能够达到肿瘤完整切除(R0切除)的胰腺癌患者,其5年生存率可达20%²3%,所以提高胰腺癌的手术切除率和R0切除率是目前胰腺癌治疗中的关键环节。胰腺癌的手术切除可能性的评估是胰腺癌治疗的第一步,该文对目前胰腺癌可切除性的评估方法进行了总结。同时,文章汇总了胰腺癌的新辅助治疗策略和相关手术技术的进展,以期对提高胰腺癌手术切除率和R0切除率的相关治疗措施有更深入的认识,进一步提高胰腺癌的整体治疗效果。     

187例Ⅱ期结直肠癌预后危险因素的相关研究及辅助化疗的疗效观察

目的 分析影响Ⅱ期结直肠癌患者预后的相关危险因素,并探讨术后辅助化疗的必要性.方法 收集2002年1月至2006年12月于我院行根治性手术治疗的Ⅱ期结直肠癌患者187例,其中男109例(58.29%),女78例(41.71%),年龄21~84岁,中位年龄63岁,平均(61.180±9.889)岁.本组患者随访期间出现复发转移57例,失访36例,到随访时间结束仍处于无病生存状态94例.随访时间22~60个月,中位随访56个月,观察术后5年无病生存率.通过SPSS 13.0统计学软件,用Kaplan-Meier法计算生存率,绘制生存曲线,对可能影响患者生存时间的因素进行单因素和COX多因素模型分析,筛选出影响预后的高危因素.对于合并高危因素的患者亚组,再按照术后是否进行辅助化疗分为两组,同样用Kaplan-Meier法和Log-rank法进行计算和检验,分析术后辅助化疗对高危Ⅱ期结直肠癌预后的影响.结果 187例Ⅱ期结直肠癌患者单因素分析,影响5年无病生存率的指标有:肿瘤低分化,淋巴结检出数目<12枚,术前合并肠梗阻,术后未辅助化疗(P<0.05);COX多因素分析:将上述单因素分析下有意义的4个变量引入COX比例风险回归模型,发现淋巴结检出数目<12枚,术前合并肠梗阻,术后无辅助化疗是影响Ⅱ期结直肠癌术后5年无病生存率的独立危险因素.亚组分析显示,发现术前合并肠梗阻,淋巴结检出数目<12枚的患者行辅助化疗的5年无病生存率高于未化疗组,差异有统计学意义(P<0.05).结论 术前合并肠梗阻,淋巴结检出数目<12枚、术后未辅助化疗是Ⅱ期结直肠癌患者预后的危险因素,而术前合并肠梗阻,淋巴结检出数目<12枚的患者可以从术后辅助化疗中获益,从而增加5年无病生存率.     

三维适形放疗联合吉西他滨区域性动脉灌注化疗治疗中晚期胰腺癌的疗效观察

目的:评价三维适形放疗联合吉西他滨区域性动脉灌注化疗对中、晚期胰腺癌的治疗效果。方法:将36例经手术病理或临床证实的晚期胰腺癌患者分为观察组、对照组各18例。两组均采用三维适形放疗,观察组加吉西他滨区域性动脉灌注化疗。观察两组疗效、生存率及毒副反应。结果:观察组总有效率,疼痛缓解程度,治疗后6、12个月生存率及中位生存时间均高于对照组(P<0.05)。结论:三维适形放疗联合吉西他滨区域性动脉灌注化疗对中、晚期胰腺癌患者能控制肿瘤生长,缓解疼痛,改善生存质量,且患者耐受良好。     

吉西他滨联合化疗在晚期胰腺癌治疗中的作用探讨

目的探讨吉西他滨联合化疗治疗晚期胰腺癌的临床疗效。方法 50例局部晚期胰腺癌患者随机分为联合化疗组25例和对照组25例,对照组使用吉西他滨单药治疗,联合化疗组应用吉西他滨联合顺铂或奥沙利铂。观察2组患者客观疗效、临床受益反应及毒副反应发生情况。结果联合化疗组疾病控制率明显高于对照组,毒副反应发生率略高于对照组。结论吉西他滨联合方案与单药治疗晚期胰腺癌比较,临床疗效相似。