BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently n...BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES: A Medline database search was performed to identify relevant articles using the keywords 'pancreatic neoplasm', and 'adjuvant therapy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identified. The results for adjuvant regimens based on systemic 5-fluorouracil with or without external radiotherapy were conflicting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS: Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.展开更多
Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response ...Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.展开更多
INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relatio...INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].展开更多
The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the develo...The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.展开更多
AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-med...AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.展开更多
OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy （CCRT） plus thalidomide.METHODS Sixty-five eligible patient...OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy （CCRT） plus thalidomide.METHODS Sixty-five eligible patients with local middle-late esophageal carcinoma were randomly assigned to the treatment group （TG） and the control group （CG）. The 33 patients from the TG were treated with CCRT plus thalidomide （a 60-70 Gy of radiation dose, and 5-FU plus cisplatin; oral administration of thalidomide at a dose of 100 mg/d on the first week and 200 mg/d on the second. Both were taken with water, at bedtime until completion of the radiotherapy. In the CG, 32 patients received CCRT only. The clinical effects and tolerance to the CCRT between the 2 groups were compared.RESULTS The response rates of the therapeutic combination in the TG and CG were 87.9% and 68.7%, respectively. There were no statistical differences in comparing the response rates between the 2 groups （P 〉 0.05）; the local control rates in the TG and CG were 93% and 91%, respectively, and there were no statistical differences between the 2 groups （P 〉 0.05）; the 1-year survival rates of the patients in the TG and CG were 74.0% and 63.0%, respectively, without statistical differences between the 2 groups （P 〉 0.05）. The improvement rates of KPS scoring in the TG and CG were 57.6% and 31.3%, respectively. There were significant differences in comparing the improvement rates between the 2 groups （P 〈 0.05）. The incidence rates of nausea and vomiting were lower in the TG compared to the CG, with a statistical significance between the 2 groups （P 〈 0.05）. However, the incidence rates of constipation, lethargy and fatigue were higher in the TG than in CG, showing a statistically significant difference between the 2 groups （P 〈 0.05）. CONCLUSION CCRT combined with thalidomide in treating esophageal carcinoma may improve the quality of life of the patients, the treatment may also raise patients＇ compliance to chemoradiotherapy, and possibly increase their long-term survival rate. Further studies related to this topic are needed.展开更多
目的系统评价替莫唑胺联合全脑放疗与单纯全脑放疗治疗恶性肿瘤脑转移的疗效和安全性。方法计算机检索Pub Med、The Cochrane Library、Web of Knowledge、中国生物医学文献数据库、中国知网和万方数据库等,收集替莫唑胺联合全脑放疗与...目的系统评价替莫唑胺联合全脑放疗与单纯全脑放疗治疗恶性肿瘤脑转移的疗效和安全性。方法计算机检索Pub Med、The Cochrane Library、Web of Knowledge、中国生物医学文献数据库、中国知网和万方数据库等,收集替莫唑胺联合全脑放疗与单纯全脑放疗治疗恶性肿瘤脑转移的随机对照试验（RCT）,检索时限均从建库至2014年3月1日,并追溯纳入研究的参考文献。由2名研究者按照纳入排除标准独立筛选文献、提取资料和质量评价后,采用Rev Man 5.2软件进行Meta分析。结果纳入10个RCT,共584例患者。Meta分析结果显示,与单纯全脑放疗比较,替莫唑胺联合全脑放疗可以提高恶性肿瘤脑转移的近期疗效（OR=4.27,95%CI：2.67~6.83,P〈0.00001）,但消化道反应较严重（OR=1.78,95%CI：1.11~2.85,P=0.02）,差异有统计学意义,在头痛（OR=1.34,95%CI：0.82~2.18,P=0.24）、白细胞（OR=1.41,95%CI：0.81~2.44,P=0.22）和血小板下降（OR=2.26,95%CI：0.82~6.20,P=0.11）方面的差异无统计学意义。结论与单纯全脑放疗比较,替莫唑胺联合全脑放疗可显著提高恶性肿瘤脑转移患者近期疗效,但同时加重消化道反应,临床应用时需结合患者具体情况进行选择。展开更多
文摘BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES: A Medline database search was performed to identify relevant articles using the keywords 'pancreatic neoplasm', and 'adjuvant therapy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identified. The results for adjuvant regimens based on systemic 5-fluorouracil with or without external radiotherapy were conflicting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS: Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.
基金supported by grants from Sanming Project of Medicine in Shenzhen(No.SZSM202211030)the Science and Technology Department Basic Research Project of Shanxi(No.202203021221284)。
文摘Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.
基金Supported in part by phone-Poulenc Rorer Pharmaceuticals INC
文摘INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].
文摘The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.
文摘AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.
文摘OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy （CCRT） plus thalidomide.METHODS Sixty-five eligible patients with local middle-late esophageal carcinoma were randomly assigned to the treatment group （TG） and the control group （CG）. The 33 patients from the TG were treated with CCRT plus thalidomide （a 60-70 Gy of radiation dose, and 5-FU plus cisplatin; oral administration of thalidomide at a dose of 100 mg/d on the first week and 200 mg/d on the second. Both were taken with water, at bedtime until completion of the radiotherapy. In the CG, 32 patients received CCRT only. The clinical effects and tolerance to the CCRT between the 2 groups were compared.RESULTS The response rates of the therapeutic combination in the TG and CG were 87.9% and 68.7%, respectively. There were no statistical differences in comparing the response rates between the 2 groups （P 〉 0.05）; the local control rates in the TG and CG were 93% and 91%, respectively, and there were no statistical differences between the 2 groups （P 〉 0.05）; the 1-year survival rates of the patients in the TG and CG were 74.0% and 63.0%, respectively, without statistical differences between the 2 groups （P 〉 0.05）. The improvement rates of KPS scoring in the TG and CG were 57.6% and 31.3%, respectively. There were significant differences in comparing the improvement rates between the 2 groups （P 〈 0.05）. The incidence rates of nausea and vomiting were lower in the TG compared to the CG, with a statistical significance between the 2 groups （P 〈 0.05）. However, the incidence rates of constipation, lethargy and fatigue were higher in the TG than in CG, showing a statistically significant difference between the 2 groups （P 〈 0.05）. CONCLUSION CCRT combined with thalidomide in treating esophageal carcinoma may improve the quality of life of the patients, the treatment may also raise patients＇ compliance to chemoradiotherapy, and possibly increase their long-term survival rate. Further studies related to this topic are needed.
文摘目的系统评价替莫唑胺联合全脑放疗与单纯全脑放疗治疗恶性肿瘤脑转移的疗效和安全性。方法计算机检索Pub Med、The Cochrane Library、Web of Knowledge、中国生物医学文献数据库、中国知网和万方数据库等,收集替莫唑胺联合全脑放疗与单纯全脑放疗治疗恶性肿瘤脑转移的随机对照试验（RCT）,检索时限均从建库至2014年3月1日,并追溯纳入研究的参考文献。由2名研究者按照纳入排除标准独立筛选文献、提取资料和质量评价后,采用Rev Man 5.2软件进行Meta分析。结果纳入10个RCT,共584例患者。Meta分析结果显示,与单纯全脑放疗比较,替莫唑胺联合全脑放疗可以提高恶性肿瘤脑转移的近期疗效（OR=4.27,95%CI：2.67~6.83,P〈0.00001）,但消化道反应较严重（OR=1.78,95%CI：1.11~2.85,P=0.02）,差异有统计学意义,在头痛（OR=1.34,95%CI：0.82~2.18,P=0.24）、白细胞（OR=1.41,95%CI：0.81~2.44,P=0.22）和血小板下降（OR=2.26,95%CI：0.82~6.20,P=0.11）方面的差异无统计学意义。结论与单纯全脑放疗比较,替莫唑胺联合全脑放疗可显著提高恶性肿瘤脑转移患者近期疗效,但同时加重消化道反应,临床应用时需结合患者具体情况进行选择。
