Phase-II Study of Gemcitabine and Cisplatin in Patients with Metastatic Biliary and Gallbladder Cancer

There is no standard chemotherapy option for patients with biliary tract cancers. These patients present fairly ill and can have a rapid progression of disease. We conducted a multi-center, phase-II trial for patients with locally unresectable or metastatic bile duct or gallbladder adenocarcinomas using a modified regimen of gemcitabine and cisplatin to potentially improve tolerability. Patients received a 21-day treatment cycle of gemcitabine at 1,000 mg/m² and cisplatin at 30 mg/m² on days 1 and 8. To participate, 33 patients signed informed consent, and 30 patients received at least one dose of chemotherapy. By intention-to-treat analyses, 7 patients (21%) experienced a partial response and another 12 (36%) had stable disease for at least 12 weeks. The median progression-free survival was 6.3 months and median overall survival was 9.7 months. After 1 year, 39% of patients were alive. Most common grade 3–4 toxicities included neutropenia (33%), thrombocytopenia (23%), anemia (20%), nausea (20%), emesis (13%) and fatigue (10%). Of note, 52% of patients withdrew from study treatment, principally due to treatment-related adverse events. We concluded that this modified regimen appeared to have comparable activity to other gemcitabine and cisplatin regimens against advanced bile duct and gallbladder cancers, but there was still moderate toxicity in this patient population.     

Outcome of Anterior Resection for Stage II Rectal Cancer Without Radiation: The Role of Adjuvant Chemotherapy

BACKGROUND This study aimed to evaluate the oncological outcome of patients who had Stage II rectal cancer and underwent curative nonsphincter-ablation surgery without adjuvant radiation.PATIENTS AND METHODS During the study period from August 1993 to December 2002, 224 patients (141 men) with Stage II cancer underwent curative anterior resection or Hartmanns procedure without adjuvant radiation. Data were collected prospectively. The oncologic outcomes of these patients were studied and the risk factors for recurrence and survival were analyzed.RESULTS The median age of the patients was 69 (range, 27–89) years and the median level of the tumor from the anal verge was 8 (range, 3–20) cm. Four patients (1.8 percent) died in the postoperative period and postoperative complications occurred in 74 patients (33 percent). The median follow-up time of the surviving patients was 43.6 months. The actuarial five-year recurrence rate was 25.4 percent, whereas the five-year actuarial local and systemic recurrence rates were 6.1 percent and 20 percent, respectively. On multivariate analysis, independent factors associated with a higher recurrence rate included lymphovascular invasion, perineural invasion, and absence of chemotherapy. The overall and cancer-specific survival rates of the patients were 71.1 percent and 81.1 percent, respectively. On multivariate analysis, only adjuvant chemotherapy (P = 0.024; hazard ratio = 6.04; 95 percent confidence interval, 1.27–28.74) and the absence of lymphovascular invasion (P = 0.002; hazard ratio = 3.77; 95 percent confidence interval, 1.63–8.77) were independent factors associated with significantly better cancer-specific survival.CONCLUSION A low local recurrence rate can be achieved in patients with Stage II rectal cancer treated with nonsphincter-ablation surgery without adjuvant radiation. Postoperative chemotherapy is associated with a lower recurrence rate and higher survival rates. Further study is warranted to define the role of adjuvant chemotherapy in patients with rectal cancer.© The American Society of Colon and Rectal SurgeonsPublished online: 28 January 2005.     

原发性肝癌的化疗与分子靶向治疗进展

原发性肝癌是我国最常见的恶性肿瘤之一,尤其以东南沿海地区为多见。高发于50岁以上年龄组,男性多于女性。自20世纪90年代以来,该病已上升为恶性肿瘤的第二位。原发性肝癌的系统性化疗和分子靶向疗法在晚期肝癌的治疗中独树一帜,有着重要的地位。     

紫杉醇联合顺铂不同给药剂量治疗老年晚期非小细胞肺癌的临床分析

目的本研究旨在比较不同剂量紫杉醇联合卡铂治疗老年晚期非小细胞肺癌(NSCLC)患者的毒副反应及疗效。方法 62例老年晚期NSCLC患者被分为结果低剂量和常规剂量两组,根据体表面积,前者给予70 mg/m2和20 mg/m2,第1、8天静滴3小时。后者给予90 mg/m2和25 mg/m2,第1、8天静滴3小时。21天为一周期,随访疗效和毒副作用。结果低剂量组和常规剂量组的总体有效率分别为45.5%与47.5%,差异没有统计学意义(P>0.05),常见的不良反应有骨髓移植、恶性呕吐、脱发等,其他不良反应,均可耐受。结论低剂量紫杉联合顺铂治疗老年晚期NSCLC疗效较好,毒副作用可以耐受,值得临床推广应用。     

重组人血管内皮抑素联合GP方案治疗非小细胞肺癌的疗效观察

目的 观察重组人血管内皮抑素联合吉西他滨+顺铂方案(GP方案)治疗非小细胞肺癌的临床疗效.方法 53例非小细胞肺癌患者随机分为对照组(26例)和治疗组(27例).对照组采用GP方案治疗;治疗组采用重组人血管内皮抑素联合GP方案治疗.治疗结束后观察两组治疗总有效率及不良反应.结果 治疗组临床总有效率为66.7%,对照组临床总有效率为46.2%,差异有显著性(P<0.05);两组毒副反应比较差异无显著性差异(P>0.05).结论 重组人血管内皮抑素联合GP方案治疗非小细胞肺癌疗效显著,能明显改善患者的生活质量,值得临床推广应用.     

非小细胞肺癌药物治疗的基因及分子生物学研究

随着肺癌的病因学研究进展,针对肺癌的药物研究也进入基因分子生物学时代.非小细胞肺癌的治疗提倡个体化治疗,即针对不同个体及致病基因,采用相应的分子靶向或化疗药物才能获得更大收益.本文总结了近年来关于非小细胞肺癌靶向基因和化疗的分子预测标志物以及相应药物的研究进展.     

进展期胃癌转移与复发的治疗进展

胃癌是最常见的恶性肿瘤之一,大多数患者在诊断时已处于进展期,胃癌的转移与复发不可避免。生物靶向药物治疗实体瘤成为当前的研究热点,新化学药物的出现使胃癌的化疗策略有了新的发展,此文从分子生物靶向治疗和化疗方面概述抗进展期胃癌转移与复发的新进展。     

丹皮酚对人大肠癌HT-29细胞增殖的抑制作用

目的探讨中药丹皮酚(Pae)对人大肠癌HT-29细胞增殖的抑制作用及其与多种化疗药物的协同作用.方法应用MTT法(噻唑蓝比色试验)检测不同浓度的丹皮酚和5-氟脲嘧啶(5-FU)、丝裂霉素(MMC)、顺铂(DDP)对体外培养的人大肠癌HT-29细胞增殖的抑制作用,同时观察低浓度的Pae与化疗药物的协同作用.结果 Pae可抑制HT-29细胞增殖,并且与药物浓度及作用时间呈正相关关系.低浓度的Pae与化疗药物协同可产生较强的抑制细胞增殖作用.结论 Pae具有直接的抗肿瘤作用,并且具有增强化疗药物作用的功效.     

Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis.     

Role of bevacizumab in colorectal cancer growth and its adverse effects:A review

Angiogenesis affects both wound healing and malignant cell growth through nutrients and oxygen.Vascular endothelial growth factor(VEGF) is the most important element involved in this complex process.Inhibition of VEGF influences angiogenesis and may restrict tumor growth and metastatic ability.Modern antiangiogenic therapy is based on this theory.Bevacizumab is a recombinant humanized monoclonal antibody(immunoglobulin G1) which binds with VEGF-A forming a large molecule.It can not be bound with VEGF tyrosine kinase receptors preventing VEGF-A incorporation;thus its activity is inhibited inducing blockage of VEGFmediated angiogenesis.Bevacizumab,in combination with chemotherapy or other novel targeted therapeutic agents,is currently used more frequently in clinical practice,mainly for managing advanced colorectal cancer.It is also used for managing other malignancies,such as breast cancer,pancreatic cancer,prostate cancer,non small-cell lung cancer,metastatic renal carcinoma and ovarian tumors.Although it is generally considered a safe treatment,there are reports of some rare side effects which should be taken into account.Recent experiments in rats and mice show promising results with a wider therapeutic range.     

乳腺癌化疗相关心脏毒性的防治研究进展

目前,心血管疾病和肿瘤的全球发病率居高不下,有数据显示,截止到2018年,全世界癌症新发总人数约为1810万例,其中,乳腺癌新发例数约为210万,占女性恶性肿瘤发病率和死亡率的首位[1]。近些年,随着我国医疗卫生服务质量和水平的不断提升,包括乳腺癌在内的癌症患者的五年生存率也相应地得到提高,乳腺癌患者整体生存时间整体延长。乳腺癌的治疗方法包括化疗、放疗、靶向治疗以及手术治疗,其中,化疗是主要的治疗手段。值得注意的是,蒽环类等化疗药物的广泛应用,虽有效提高了乳腺癌患者的远期生存率,但同时也不可避免地带来了心律失常、心力衰竭、心肌病等一系列心血管毒性反应,不仅在一定程度上限制了这些药物的临床应用,也对乳腺癌幸存患者的远期预后以及生活质量造成了严重不良影响。因此,乳腺癌化疗相关的心脏毒性有必要引起心血管及肿瘤科医师的警惕和重视,本文现就乳腺癌化疗相关心脏毒性的防治研究进展做一综述。     

Urothelial cancer of bladder in young versus older adults: Clinical and pathological characteristics and outcomes

Bladder urothelial carcinoma is rare in young adults and occurs more commonly in older individuals. The aim of this study was to compare the clinical behavior, pathologic characteristics, and prognosis of urothelial carcinoma of urinary bladder in young versus older adults. A retrospective review of our records between 2007 and 2013 identified 56 patients (42 males and 14 females) with transitional cell carcinoma of the bladder who were less than 40 years old. Clinical and pathological parameters of patients who were less than 40 years of age were compared with those of a series of patients older than 40 years of age (the control group) during the same period. A survival analysis was performed using the Kaplan–Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinical outcomes. The mean age was 29.21 years (range, 5–40 years) for patients less than 40 years old and 61.66 years (range, 41–75) for those older than 40 years. The mean follow-up was 40.26 months (range, 12–65 months) for young patients and 42.57 months (range, 12–72 months) for the older patients. Young bladder cancer patients had smaller-sized tumors (less than 3 cm), less high-grade cancers, higher papillary urothelial neoplasms of low malignant potential, and low-grade tumors than patients older than 40 years. Multivariate logistic regression analysis predicted tumor recurrence in young patients with high-grade tumors [odds ratio (OR), 1.959; 95% confidence interval (CI), 1.235–2.965; p = 0.046] and tumors larger than 3 cm (OR, 1.772; 95% CI, 1.416–1.942; p = 0.032). The 5-year overall survival rate was 100% for young patients and 88.1% for older patients. No difference was observed in the recurrence-free (p = 0.321) and progression-free (p = 0.422) survival rates between the two groups. We concluded that although the clinical stage distribution, natural history, and outcomes of bladder urothelial cancer in young adults are similar to those in their older counterparts, clinicians must be aware that patients under 40 years of age presented with higher-grade and larger (>3 cm) tumors and are more likely to experience tumor recurrence.     

Toxicity Profile and Efficacy of Oral Capecitabine as Adjuvant Chemotherapy for Chinese Patients with Stage III Colon Cancer

Purpose The Xeloda in Adjuvant Cancer Therapy trial, conducted in a white population of patients, established capecitabine (Xeloda) as adjuvant chemotherapy for Stage III colon cancer. Given the ethnical difference in toxicity of adjuvant chemotherapy in colon cancer, this study was designed to evaluate the safety and efficacy of adjuvant capecitabine in Chinese patients with colon cancer. Methods Chinese patients with curatively resected Stage III colon adenocarcinoma, who received adjuvant capecitabine, were entered into a prospective database. Oral capecitabine was given at 1,250 mg/m² twice daily, Days 1 to 14, every 21 days, for 8 cycles. Toxicities, laboratory abnormalities, and survival outcomes were evaluated. Results Fifty-eight patients were entered into the database between August 2004 and October 2005. The median age was 63.9 years with a male-to-female ratio of 1.15:1. With a median follow-up duration of 20.9 months, 14 patients relapsed and 3 patients died. Disease-free and overall survival at two years was 69 and 97 percent, respectively. Grade 3 toxicities occurred as follows: stomatitis (1.7 percent), diarrhea (0 percent), hand-foot syndrome (41.4 percent), leucopenia (1.7 percent), neutropenia (3.4 percent), and hyperbilirubinemia (1.7 percent). No Grade 4 or 5 toxicity was noted. Compared with the Xeloda in the Adjuvant Cancer Therapy trial, a much higher incidence of serious hand-foot syndrome and a lower rate of severe diarrhea were found in this study. Conclusions A different toxicity profile of adjuvant capecitabine was noted in this study on Chinese patients with colon cancer compared with that reported in the Xeloda in Adjuvant Cancer Therapy trial, whereas the efficacy outcomes were comparable. Presented in part at the Asian Oceanian Congress of Radiology, August 6 to 9, 2006.     

Continued Survival of More Than Ten Years, Without Resection of Metastatic Disease, in Patients With Metastatic Colorectal Cancer Treated With Biomodulated Fluorouracil: Report of Two Cases

The treatment of metastatic colorectal cancer by chemotherapy alone was considered palliative and without the potential to cure patients unless patients were rendered resectable. We report two patients with metastatic colorectal cancer involving the liver who were considered inoperable and were treated with systemic chemotherapy using biomodulated 5-fluorouracil. Both patients received 5-fluorouracil and N-(phosphonoacetyl)-l-aspartic acid; one also received methotrexate, leucovorin, and triacetyluridine with the N-(phosphonoacetyl)-l-aspartic acid and 5-fluorouracil. Both patients had a complete remission with chemotherapy and are still alive with no evidence of cancer ten years after the diagnosis of unresectable metastatic disease. These patients provide evidence that prolonged survival can be achieved withsystemic chemotherapy without the use of surgery or other forms of local therapy. These patients also confirm the importance of continued investigation of fluorouracil modulating agents, which may further enhance the recent progress made with fluorouracil-based combination chemotherapy for colorectal cancer.     

Carcinoma of pancreatic body and tail: are there improvements in diagnosis and treatment modalities over the past decade?

BACKGROUND AND AIM OF STUDY: The aim of the present study is to assess whether or not there has been improvement in the therapeutic strategy for body-tail pancreatic carcinoma over the past decade. PATIENTS AND METHODS: A total of 215 patients suffering from cytologically and histologically documented ductal carcinoma in the pancreatic body-tail, observed from 1990 to 1999, were analysed. Changes in tumour stage at diagnosis, in the percentage of patients treated surgically, in resectability rates and in the use of anticancer therapies over the years were sought. Survival curves were evaluated in relation to the treatments adopted. RESULTS: Over the 10-year period, no significant differences were observed with respect to the stage at diagnosis, resectability or type of surgery adopted. There was a significant increase in the percentage of unoperated patients (p < 0.0001) and, as expected, in the percentages of patients submitted to chemo- and/or radiotherapy (p < 0.0001). With the sole exception of tumour stage in the case of patients undergoing radiotherapy, a comparison between groups revealed no element of patient selection bias other than time. The survival of patients undergoing chemotherapy is significantly better, also at multivariate analysis, than that of patients not undergoing such therapy (13 vs. 5.8 months; p < 0.0001). CONCLUSIONS: There has been no change over the years in the direction of earlier diagnosis and the prognosis remains distinctly poor. More extensive use of anticancer therapies, however, has led to a significant increase in median survival. Radical resection, when possible, assures the longest survival.     

蒽环类药物及其新剂型在晚期胃癌化疗中的价值

胃癌治疗的关键在于早期诊断和及时行根治性切除术。我国的胃癌发病率高,且多数患者在确诊时已进入中晚期,因此以化疗为主的综合治疗是其主要治疗手段。化疗可延长晚期胃癌患者的生存期,提高生活质量。蒽环类药物参与的多种化疗方案在晚期胃癌的治疗中有一定效果。随着脂质体等新剂型研究的日益深入．有望进一步降低蒽环类药物的不良反应,提高其临床应用价值。     

整合素在胃癌侵袭转移及靶向药物治疗中的研究进展

整合素作为黏附分子中的一大类家族,广泛的参与机体的各种病理生理活动,包括细胞生存、生长、分化、迁移、炎症反应、血小板聚集、组织修复以及肿瘤侵袭转移等多个过程.自整合素发现20多年来,已有许多整合素介导的靶向药物相继应用于临床,而且每年有更多新的药物进行临床试验,其中有些药物显示出广阔的临床应用前景.此外,基于整合素在肿...     

Plasminogen Activator Inhibitor Type-1 (Part Two): Role for Failure of Thrombolytic Therapy. PAI-1 Resistance as a Potential Benefit for New Fibrinolytic Agents

Rapid and sustained reperfusion of an occluded coronary artery is the goal of thrombolytic therapy in acute myocardial infarction. However, the clot-dissolving efficacy of fibrinolytic agents such as tissue-type plasminogen activator (t-PA) is limited, in vivo, in part by the action of plasminogen activator inhibitor type-1 (PAI-1). A new generation of fibrinolytic agents has been genetically engineered to have greater resistance to PAI-1 inhibition. This articlereviews the pathophysiologic role of PAI-1 in failureof thrombolytic therapy and describes the advantages that PAI-1-resistance may confer uponfibrinolytic agents such as TNK-t-PA, the new fibrinolytic agent with the most powerful PAI-1 resistance.