归脾汤结合TF方案用于晚期胃癌的临床观察
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摘要
目的:在世界范围内,胃癌是第四高发的恶性肿瘤,而死亡率则高居第二位。中国的许多地区位居恶性肿瘤发病率和死亡率的第一位。胃癌的早期诊断率低,临床上发现的胃癌大多为中晚期。手术切除是胃癌治疗的首选方法。但约40%的患者就诊时已经为晚期,失去手术机会;50%左右的胃癌根治术后患者出现复发转移。晚期胃癌患者预后差,仅行支持治疗的患者中位生存期约3～5个月。目前尚缺乏足够证据支持胃癌术后辅助化疗对生存期的益处,晚期胃癌最佳一线化疗方案尚无定论。已有多项随机临床试验发现,与最佳支持治疗相比,化疗可使中位生存期由3～5个月延长至7.5～l2个月。化疗可延长患者生存期。但化疗在控制肿瘤进展,延长生存期的同时会对机体产生不同程度损害和不良反应。中药可增加化疗疗效、提高生存期、减轻化疗不良反应。本文研究的目的是探讨对于晚期胃癌患者,TF方案化疗结合归脾汤加减治疗能否提高近期疗效、延长生存期及减轻化疗不良反应。
方法:收集大连医科大学附属二院肿瘤科2006年7月～2008年12月经病理证实的72例Ⅳ期胃癌患者的病例资料,将患者随机分为治疗组及对照组,治疗组采用TF(PTX +5-Fu+CF,紫杉醇+5-氟尿嘧啶+亚叶酸钙)方案化疗结合归脾汤加减治疗,归脾汤主要成分:党参20g,炒白术15g,黄芪25g,甘草10g,茯苓20g,远志10g,炒枣仁15g,龙眼肉10g,当归10g,木香10g,大枣10g。化疗期间服用归脾汤,化疗间歇期以归脾汤为主方,根据病人的病理基础,气滞血瘀者加用化瘀散结药物,如郁金、莪术等;痰湿盛、舌苔厚腻者加用健脾、祛湿化痰药物,如薏米、瓜蒌等;伴热毒者加用清热解毒药物,如半枝莲、淡竹叶等;胃阴亏乏者加用麦冬、沙参等;腹痛气滞者加用柴胡、川楝子等。归脾汤加减治疗疗程分别为2个月～28个月。TF方案具体用药:PTX:90 mg/㎡静滴第1,8天;CF:200mg静滴第1-2天;5-Fu:400 mg/㎡.d静推,600 mg/㎡.d持续静滴22小时,第1-2天;每21天1周期。对照组采用TF方案化疗。两组对比观察患者近期疗效、生存期及不良反应发生情况。近期疗效按实体瘤客观疗效评价RECIST(Response Evaluation Criteria In Solid Tumors)标准[2]评价,不良反应根据美国国立肿瘤研究所(NCI)抗癌药急性和亚急性毒性表现和分级标准CTCAE3.0版(Common Terminology Criteria for Adverse Events v3.0)进行判断?采用SPSS13.0统计软件进行分析,两组有效率比较采用X2检验,生存期采用Kaplan-Meier方法分析,Log-rank方法检验,P<0.05有统计学意义?
结果:
1. 72例晚期胃癌患者中,按RECIST标准可以评价疗效,治疗组患者有效率42%;对照组有效率35.2%。虽然近期疗效治疗组优于对照组,但两组差异无统计学的显著意义(P>0.05)。
2. 72例晚期胃癌患者中,70例患者可评价中位生存期,治疗组患者37例,平均生存期11个月,1年生存率39.5%;对照组33例,平均生存期9个月,1年生存率26.5%。生存期比较显示治疗组优于对照组(P﹤0.05)。
3.治疗组不良反应主要表现为骨髓抑制、恶心呕吐反应,其中骨髓抑制Ⅰ度占47%,Ⅱ度占42%,Ⅲ+Ⅳ度占11%;恶心?呕吐多为Ⅰ度,占72%,Ⅱ度占23%,Ⅲ+Ⅳ度占5%;对照组不良反应主要表现同治疗组,但较治疗组为重。其中骨髓抑制Ⅰ度占38%,Ⅱ度占32%,Ⅲ+Ⅳ度占30%;恶心呕吐Ⅰ度占53%,Ⅱ度占26%,Ⅲ+Ⅳ度占21%。两组对照有统计学的显著意义(P<0.05)。
结论
1. TF方案结合归脾汤加减治疗与单独应用TF方案相比较,有生存优势,可延长生存期。
2. TF方案化疗结合归脾汤加减治疗晚期胃癌时耐受性良好,不良反应主要表现为骨髓抑制、恶心呕吐,大多为Ⅰ～Ⅱ度,易于控制,在减轻化疗不良反应方面有优势。
Objective: The incidence of gastric cancer is in the fourth place among all the malignant tumors worldwide, and the mortality rate is in the second place. But in many regions of China, the morbidity and mortality of gastric cancer is in the first place. Due to the low rate of early diagnosis, most of the clinical diagnosis of gastric cancer is in the advanced stage. The preferred treatment of gastric cancer is surgical resection. However, about 40% of patients lost the opportunities of surgery because of the late stage of the cancer; about 50% of gastric cancer patients appeared recurrence and metastasis after radical resection. The prognosis of advanced gastric cancer is poor, and the meso survival time is about 3 to 5 months if the patients only adopt support the treatment. There is no sufficient evidence to support that the postoperative adjuvant chemotherapy is benefit for gastric cancer survival, and the best first-line chemotherapy program for advanced gastric cancer is still undetermined. Many randomized clinical trial found that chemotherapy prolong the median survival time from 3~5 months to 7.5~l2 months compared with best supportive care. Chemotherapy can prolong the patients’life span but induce disadvantage and adverse effect at different level during the process of controlling progression of tumor. The traditional Chinese medicine may increase the chemotherapeutic efficacy, improve survival time and reduce the side effects of chemotherapy. The purpose of this paper is to explore the effect of combination of TF and decoction for invigorating the spleen for the treatment of advanced gastric cancers on the aspect of improving the short-term effect, extending the survival time and reducing the adverse effects of chemotherapy.
Methods:The data of 72 cases of pathologically confirmed stageⅣgastric cancer from July, 2006 to Dec, 2008 were collected in the Oncological Department of Second Affiliated Hospital of Dalian Medical University and were randomly divided into treatment group and control group. The treatment group adopt the chemotherapy of TF (PTX +5 -Fu + CF, Paclitaxel +5- fluorouracil + calcium folinate) combined with decoction for invigorating the spleen treatment. The essential components of decoction for invigorating the spleen are dangshen 20g, Atractylodes macrocephala 15g, Radix Astragali 25g, Licorice 10g, Poria 20g, Polygala 10g , speculation semen ziziphi spinosae 15g, longan meat 10g, Chinese angelica 10g, Radix 10g, jujube 10g. The decoction for invigorating the spleen was adopted during chemotherapy and during the intermission of chemotherapy, the decoction was used as main prescription. according to the pathological base, the patient with qi-stagnancy and blood stasis added drugs of removing blood and stasis, such as curcumae, radix and curcumae etc.; the patient with phlegmatic hygrosis and thick libngual fur added drugs of invigorating the spleen, dehygrosis and apophlegmatisant such as Coix lacryma and snakegourd fruit etc.; the patient with pyretic toxicity added drugs of heat-clearing and detoxicating, such as scutellaria barbata, lophatherum herb, etc.; the patient with fluid in stomach deficiency added drugs of ophiopogonis tuber, root of straight ladybell, etc.; the patient with abdominal pain and qi-stagnancy added drugs of bupleurum chinense, ructus meliae toosendan etc.. The course of decoction for invigorating the spleen treatment was 2 months to 28 months. TF specific medication program: PTX: 90 mg / m2 intravenous infusion on the 1st and 8th days; CF: 200mg intravenous infusion on the first 1-2 days; 5-Fu: 400 mg /㎡.d intravenous injection, 600 mg /㎡.d 22 hours continuous infusion on the first 1～2 days. Every 21 days was 1 cycle. The control group adopted chemotherapy with TF program. The short-term effect, survival time and the incidence of adverse reactions of the two groups were comparative observed. Clinical efficacy was objectively evaluated according to the RECIST criteria (Response Evaluation Criteria In Solid Tumors) and the adverse reactions were evaluated with the Common Terminology Criteria for Adverse Events v3.0 (CTCAE3.0) of anticancer drug in acute and subacute toxicity in United States National Cancer Institute (NCI). SPSS13.0 statistical software was adopted with X2 test to analyze the efficiency of the two groups and the Kaplan-Meier and Log-rank test to analyze survival time, P<0.05 showed statistical significance.
Results:
1. The therapeutic effects of 72 cases of advanced gastric cancers were evaluated by RECIST criteria. The efficiency was 42% and 35.2% in the treatment group and control group. There is no significant statistical difference between the two groups (P>0.05) although the short-term efficacy of the treatment group was better than that of the control group.
2. Among the 72 cases of advanced gastric cancer patients, 70 cases were evaluable in the median survival time, of which 37 cases of treatment group with the average survival period of 11 months and 1-year survival rate of 39.5%; and 33 cases of control group, the average survival period of 9 months, 1-year survival rate of 26.5%. The survival time of the treatment group showed significant advantage than that of the control group (P <0.05).
3. The main adverse reactions of treatment group were myelo- suppression, nausea and vomiting. Among the bone marrow suppression cases, 47% were degreeⅠ, 42% were degreeⅡand 11% were degreeⅢ+Ⅳ; for nausea and vomiting cases, most were degreeⅠ, accounting for 72%, 23% were degreeⅡ, and 5% were degreeⅢ+Ⅳ. The main adverse reactions of control group were similar with the treatment group, but more severe. Among the bone marrow suppression cases, 38% were degreeⅠ, 32% were degreeⅡand 30% were degreeⅢ+Ⅳ; for nausea and vomiting cases, 53% were degreeⅠ, 26% were degreeⅡand 21% were degreeⅢ+Ⅳ. The significant statistical difference could be established between the two groups (P <0.05).
Conclusion:
1. The combination treatment of TF program and decoction for invigorating the spleen demonstrates a survival advantage to extend survival time compared with separate application of program TF.
2. The combination treatment of TF program and decoction for invigorating the spleen showed well tolerance in the treatment of advanced gastric cancer. The main adverse reactions were myelosuppression, nausea and vomiting, most of which wereⅠ~Ⅱdegrees that easy to control and presenting advantages in mitigating the adverse effects of chemotherapy.
方法:收集大连医科大学附属二院肿瘤科2006年7月～2008年12月经病理证实的72例Ⅳ期胃癌患者的病例资料,将患者随机分为治疗组及对照组,治疗组采用TF(PTX +5-Fu+CF,紫杉醇+5-氟尿嘧啶+亚叶酸钙)方案化疗结合归脾汤加减治疗,归脾汤主要成分:党参20g,炒白术15g,黄芪25g,甘草10g,茯苓20g,远志10g,炒枣仁15g,龙眼肉10g,当归10g,木香10g,大枣10g。化疗期间服用归脾汤,化疗间歇期以归脾汤为主方,根据病人的病理基础,气滞血瘀者加用化瘀散结药物,如郁金、莪术等;痰湿盛、舌苔厚腻者加用健脾、祛湿化痰药物,如薏米、瓜蒌等;伴热毒者加用清热解毒药物,如半枝莲、淡竹叶等;胃阴亏乏者加用麦冬、沙参等;腹痛气滞者加用柴胡、川楝子等。归脾汤加减治疗疗程分别为2个月～28个月。TF方案具体用药:PTX:90 mg/㎡静滴第1,8天;CF:200mg静滴第1-2天;5-Fu:400 mg/㎡.d静推,600 mg/㎡.d持续静滴22小时,第1-2天;每21天1周期。对照组采用TF方案化疗。两组对比观察患者近期疗效、生存期及不良反应发生情况。近期疗效按实体瘤客观疗效评价RECIST(Response Evaluation Criteria In Solid Tumors)标准[2]评价,不良反应根据美国国立肿瘤研究所(NCI)抗癌药急性和亚急性毒性表现和分级标准CTCAE3.0版(Common Terminology Criteria for Adverse Events v3.0)进行判断?采用SPSS13.0统计软件进行分析,两组有效率比较采用X2检验,生存期采用Kaplan-Meier方法分析,Log-rank方法检验,P<0.05有统计学意义?
结果:
1. 72例晚期胃癌患者中,按RECIST标准可以评价疗效,治疗组患者有效率42%;对照组有效率35.2%。虽然近期疗效治疗组优于对照组,但两组差异无统计学的显著意义(P>0.05)。
2. 72例晚期胃癌患者中,70例患者可评价中位生存期,治疗组患者37例,平均生存期11个月,1年生存率39.5%;对照组33例,平均生存期9个月,1年生存率26.5%。生存期比较显示治疗组优于对照组(P﹤0.05)。
3.治疗组不良反应主要表现为骨髓抑制、恶心呕吐反应,其中骨髓抑制Ⅰ度占47%,Ⅱ度占42%,Ⅲ+Ⅳ度占11%;恶心?呕吐多为Ⅰ度,占72%,Ⅱ度占23%,Ⅲ+Ⅳ度占5%;对照组不良反应主要表现同治疗组,但较治疗组为重。其中骨髓抑制Ⅰ度占38%,Ⅱ度占32%,Ⅲ+Ⅳ度占30%;恶心呕吐Ⅰ度占53%,Ⅱ度占26%,Ⅲ+Ⅳ度占21%。两组对照有统计学的显著意义(P<0.05)。
结论
1. TF方案结合归脾汤加减治疗与单独应用TF方案相比较,有生存优势,可延长生存期。
2. TF方案化疗结合归脾汤加减治疗晚期胃癌时耐受性良好,不良反应主要表现为骨髓抑制、恶心呕吐,大多为Ⅰ～Ⅱ度,易于控制,在减轻化疗不良反应方面有优势。
Objective: The incidence of gastric cancer is in the fourth place among all the malignant tumors worldwide, and the mortality rate is in the second place. But in many regions of China, the morbidity and mortality of gastric cancer is in the first place. Due to the low rate of early diagnosis, most of the clinical diagnosis of gastric cancer is in the advanced stage. The preferred treatment of gastric cancer is surgical resection. However, about 40% of patients lost the opportunities of surgery because of the late stage of the cancer; about 50% of gastric cancer patients appeared recurrence and metastasis after radical resection. The prognosis of advanced gastric cancer is poor, and the meso survival time is about 3 to 5 months if the patients only adopt support the treatment. There is no sufficient evidence to support that the postoperative adjuvant chemotherapy is benefit for gastric cancer survival, and the best first-line chemotherapy program for advanced gastric cancer is still undetermined. Many randomized clinical trial found that chemotherapy prolong the median survival time from 3~5 months to 7.5~l2 months compared with best supportive care. Chemotherapy can prolong the patients’life span but induce disadvantage and adverse effect at different level during the process of controlling progression of tumor. The traditional Chinese medicine may increase the chemotherapeutic efficacy, improve survival time and reduce the side effects of chemotherapy. The purpose of this paper is to explore the effect of combination of TF and decoction for invigorating the spleen for the treatment of advanced gastric cancers on the aspect of improving the short-term effect, extending the survival time and reducing the adverse effects of chemotherapy.
Methods:The data of 72 cases of pathologically confirmed stageⅣgastric cancer from July, 2006 to Dec, 2008 were collected in the Oncological Department of Second Affiliated Hospital of Dalian Medical University and were randomly divided into treatment group and control group. The treatment group adopt the chemotherapy of TF (PTX +5 -Fu + CF, Paclitaxel +5- fluorouracil + calcium folinate) combined with decoction for invigorating the spleen treatment. The essential components of decoction for invigorating the spleen are dangshen 20g, Atractylodes macrocephala 15g, Radix Astragali 25g, Licorice 10g, Poria 20g, Polygala 10g , speculation semen ziziphi spinosae 15g, longan meat 10g, Chinese angelica 10g, Radix 10g, jujube 10g. The decoction for invigorating the spleen was adopted during chemotherapy and during the intermission of chemotherapy, the decoction was used as main prescription. according to the pathological base, the patient with qi-stagnancy and blood stasis added drugs of removing blood and stasis, such as curcumae, radix and curcumae etc.; the patient with phlegmatic hygrosis and thick libngual fur added drugs of invigorating the spleen, dehygrosis and apophlegmatisant such as Coix lacryma and snakegourd fruit etc.; the patient with pyretic toxicity added drugs of heat-clearing and detoxicating, such as scutellaria barbata, lophatherum herb, etc.; the patient with fluid in stomach deficiency added drugs of ophiopogonis tuber, root of straight ladybell, etc.; the patient with abdominal pain and qi-stagnancy added drugs of bupleurum chinense, ructus meliae toosendan etc.. The course of decoction for invigorating the spleen treatment was 2 months to 28 months. TF specific medication program: PTX: 90 mg / m2 intravenous infusion on the 1st and 8th days; CF: 200mg intravenous infusion on the first 1-2 days; 5-Fu: 400 mg /㎡.d intravenous injection, 600 mg /㎡.d 22 hours continuous infusion on the first 1～2 days. Every 21 days was 1 cycle. The control group adopted chemotherapy with TF program. The short-term effect, survival time and the incidence of adverse reactions of the two groups were comparative observed. Clinical efficacy was objectively evaluated according to the RECIST criteria (Response Evaluation Criteria In Solid Tumors) and the adverse reactions were evaluated with the Common Terminology Criteria for Adverse Events v3.0 (CTCAE3.0) of anticancer drug in acute and subacute toxicity in United States National Cancer Institute (NCI). SPSS13.0 statistical software was adopted with X2 test to analyze the efficiency of the two groups and the Kaplan-Meier and Log-rank test to analyze survival time, P<0.05 showed statistical significance.
Results:
1. The therapeutic effects of 72 cases of advanced gastric cancers were evaluated by RECIST criteria. The efficiency was 42% and 35.2% in the treatment group and control group. There is no significant statistical difference between the two groups (P>0.05) although the short-term efficacy of the treatment group was better than that of the control group.
2. Among the 72 cases of advanced gastric cancer patients, 70 cases were evaluable in the median survival time, of which 37 cases of treatment group with the average survival period of 11 months and 1-year survival rate of 39.5%; and 33 cases of control group, the average survival period of 9 months, 1-year survival rate of 26.5%. The survival time of the treatment group showed significant advantage than that of the control group (P <0.05).
3. The main adverse reactions of treatment group were myelo- suppression, nausea and vomiting. Among the bone marrow suppression cases, 47% were degreeⅠ, 42% were degreeⅡand 11% were degreeⅢ+Ⅳ; for nausea and vomiting cases, most were degreeⅠ, accounting for 72%, 23% were degreeⅡ, and 5% were degreeⅢ+Ⅳ. The main adverse reactions of control group were similar with the treatment group, but more severe. Among the bone marrow suppression cases, 38% were degreeⅠ, 32% were degreeⅡand 30% were degreeⅢ+Ⅳ; for nausea and vomiting cases, 53% were degreeⅠ, 26% were degreeⅡand 21% were degreeⅢ+Ⅳ. The significant statistical difference could be established between the two groups (P <0.05).
Conclusion:
1. The combination treatment of TF program and decoction for invigorating the spleen demonstrates a survival advantage to extend survival time compared with separate application of program TF.
2. The combination treatment of TF program and decoction for invigorating the spleen showed well tolerance in the treatment of advanced gastric cancer. The main adverse reactions were myelosuppression, nausea and vomiting, most of which wereⅠ~Ⅱdegrees that easy to control and presenting advantages in mitigating the adverse effects of chemotherapy.
引文
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[27] Suzuki S, Harada N, Takeo Y, et al. Bi- weekly irinotecan hydrochloride and cisplatin as a second-line chemotherapy for patients with advanced gastric cancer. Gan To Kagaku Ryoho,2007,34:2245-2248.
[28] Chun JH, Kim HK, Lee JS, et al. Weekly irinotecan in patients with metastatic gastric cancer failing cisplatin-based chemotherapy. Jpn J Clin Oncol,2004, 34:8-13.
[29] Catalano V, Graziano F, Salvagni S.. Lack of resistance to oxaliplatin(L-OHP)-based chemotherapy in patients (pts) with advanced gastric cancer previously treated with cisplatin-containing regimens:preliminary results of a phaseⅡstudy. Proc Am Soc Clin Oncol 21:2002(abstr 2200).
[30] Oh SC, Kim Y, Kim J, PhaseⅡtrial of oxalioplatin, 5-FU, and leucovorin chemotherapy for the previously treated pa-tients with advanced gastric cancer. Journal of Clinical Oncology,2007,25:15138s.
[31] Seo HY, Kim DS, Choi YS, et al. Treatment outcomes of oxaliplatin, 5-FU,and leucovorin as salvage therapy for pa-tients with advanced or metastatic gastric cancer: a retrospective analysis. Cancer Chemother Pharmacl, 2008 Apr
[32] Kim Y, Park S, Park J, et al. Oxaliplatin, 5-fluorouracil, and leuvocorin and (FOLFOX-4) combination chemo-therapy as salvage treatment in pretreated patients with advanced gastric cancer(AGC). J Clin Oncol,2008,26:1577s.
[33] Nagashima F,Boku N,Ohtsu A,et al.Biological Markers as a Predictor forResponse and Prognosisof Unresectable Gastric Cancer Patients Treated with Irinotecan and Cisplatin.Jpn J Clin Oncol,2005,35:714-719
[34] Wei J, Aou Z, Qian X. ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOL-FOX regimen.Br J Cancer, 2008, 98:1398-1402.
[35]金晶,李晔雄,局部进展期胃癌的综合治疗癌症进展杂志,2007,5:131-142.
[36] Macdonald JS,Smalley S,Benedetti J,et al.Postoperation conbination radiation and chemotherapy improves disease-free survival (DFS)and overall survival (OS) inresected adenocarcinoma of the stomach and G.E.junction .Results of intergroup study INT-0116 (SWOG 9008).Proc Am Soc Clin Oncol,2000, 19: 387-395.
[37] Kim S,Lim DH,Lee J,et al.An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach.Int-J-Radiat-Oncol-Biol-Phys,2005,63:1279-1285.
[38]李佩文.中药预防肿瘤转移的可能途径.第八届全国中西医结合肿瘤学术会议论文集(青岛),2000:171
[39]李锦毅。中药诱导细胞凋亡抗肿瘤转移治疗中的可能机制.辽宁中医杂志,1998(25~9):399
[40]李佩文主编。恶性肿瘤的术后治疗.人民卫生出版社.2002:l119
[41]王志学.中医药抗肿瘤转移治疗的思路与方法探讨.山东中医杂志.1997,16(12):532
[42]沈朝萍,刘锦霞,马兰花,等.浅谈活血化瘀中药抗肿瘤转移的思路与应用.国医论坛,2001,16(4):12
[43]李佩文.中药预防肿瘤转移的可能途径.中医杂志,1999,40(2):116
[44] [45]扬振江.活血化瘀对肿瘤转移影响的研究概况.湖南中医学院学报,2002,22(4):67
[46]王寅,潭侃,程明和等.中药防治肿瘤转移的研究进展.中草药, 2002,33(10).附3
[47]李忠主编.临床中医肿瘤学.第1版.辽宁科学技术出版社,2002:288~293
[48]扬新中.中医药防治肿瘤转移的思路。湖北中医药杂志,2002,24(8): 8
[49]李家庚,屈松柏主编.中医肿瘤防治大全.科学技术文献出版社,1994:584～588
[50]李佩文.恶性肿瘤的术后治疗.人民卫生出版社,2002:118
[51]王寅,潭侃,程明和,等.中药防治肿瘤转移的研究进展.中草药, 2002I 33(10).附3
[52]郑玉玲,韩新巍主编.中西医肿瘤诊疗大全.中国中医药出版社,1996:807
[53]王希胜,陈光伟,李仁廷,等.山仙颗粒抗肿瘤的临床与实验研究[J].陕西中医学院学报,2002,25(3):47—49.
[54]陈光伟.中医减轻恶性肿瘤放化疗毒副反应的作用[J].陕西中医学院学报,1999,22(5):56—57.
[55]金岚,金若敏.新编中药药理与临床应用[M].上海:上海科学技术文献出版社,1995.21:238,273,345,389.
[56]刘海金,蔡琦,曾祥福,艾迪注射液减轻胃肠癌化疗毒副作用的临床观察[J].赣南医学院学报,2002,25(1):86-87
[57]冷毓青,杨震玲,肖月升,等黄芪党参蘑菇煎对晚期食管癌胃癌化疗的免疫调节作用临床研究[J].时珍国医国药,2008,19(6):1474-1475
[58]杨晓慧陈焕朝中西医结合治疗晚期胃癌临床观察[J].肿瘤防治研究, 1999,26(6):426-427
[59]杨志新,尤建良中药微调3号辨证治疗晚期胃癌临床研究[J].辽宁中医杂志2006,33(11):1434-1435
[60]陈曦扶正消瘤汤治疗中晚期胃癌46例临床观察[J].航空航天医药,2008,19(2):99
[61]任立新,王亚红,哈敏文.华蟾素治疗晚期胃癌的临床疗效研究[J].中国中药杂志,2008,33(12):1474-1475
[62]宋洪恩.三参化瘀汤及拔毒攻坚散治疗胃癌93例.上海中医药杂志, 1997,(5):27.
[63]天伟.参芪注射液在胃癌化疗中的增效与减毒作用.北京中医药大学学报,1997,20(1):53.
[1] Yang L. Incidence and nortaliy of gastric cancer in China. World J Gastroenterol , 2006 , 12:17-20.
[2] Tsuchida Y,Therasse P.Response evaluation criteria in solid tumors (RECISq"): New guiddines J.Mc_d Pediatr Oncol,2001,37(1):1.
[3] Cancer Therapy Evaluation Program,Common Terminology Criteria for Adverse Events,Version 3.0,DCTD,NCI,NIH,DHHS.March 31,2003 (http://ctep.cancer. gov), Publish Date:August 9,2006
[4] Bang YJ,Kang WK,Kang YK et al.Docetaxel 75 mg/㎡ is active and well tolerated in patients with metastatic or recurrent gastric cancer:a phase II trial.Jpn J Clin Oncol 2002;32:248–254.
[5] Ohtsu A,Boku N,Tamura F et al.An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer.Am J Clin Oncol 1998;21:416–419.
[6] Sulkes A,Smyth J,Sessa C et al.Docetaxel (Taxotere) in advanced gastric cancer:results of a phase II clinical trial.EORTC Early Clinical Trials Group.Br J Cancer 1994;70:380–383.
[7] Ajani JA,Fairweather J,Dumas P et al.Phase II study of Taxol in patients with advanced gastric carcinomas.Cancer J Sci Am 1998;4:269–274.
[8] inzig AI,Neuberg D,Remick SC et al.Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy:the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293.Med Oncol 1996;13:87–93.
[9] Garcia AA,Leichman CG,Lenz HJ etal.Phase II trial of out patient schedule of paclitaxel in patients with previously untreated metastatic,measurable adeno- carcinoma of the stomach.Jpn J Clin Oncol 2001;31:275–278.
[10] Kim TW,Kang YK,Ahn JH et al.Phase II study of capecitabine plus cis-platin as first-line chemotherapy in advanced gastric cancer.Ann Oncol 2002;13:1893– 1898.
[11] Kollmannsberger C,Quietzsch D,Haag C et al.A phase II study of paclitaxel, weekly,24-hour continuous infusion 5-fluorouracil,folinic acid and cisplatin in patients with advanced gastric cancer.Br J Cancer 2000;83:458–462.
[12] Ryoo BY,Kim TW,Choi SJ et al.A phase II trial of paclitaxel (T) and carboplatin (C) for advanced gastric cancer refractory to 5-fluorouracil (F) and cisplatin/ heptaplatin (P).Proc Am Soc Clin Oncol 2001;20:128.
[13] Honecker F,Kollmannsberger C,Quietzsch D et al.Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil,folinic acid and 3-weekly cisplatin for the treatment of patients with advanced gastric cancer.Anticancer Drugs 2002;13:497–503.
[14] Gadgeel SM,Shields AF,Heilbrun LK et al.Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer.Am J Clin Oncol 2003; 26:37–41.
[15] Muard AM,Petroianu A,Guimaraes RC,et al.PhaseⅡtrial of the combination of paclitaxel and 5-fluorouracil in the treatment of advanced gastric cancer:a novel,safe,and effective regimen.Am J Clin Oncol 1999; 22(6):580
[16]冷毓青,杨震玲,肖月升,等黄芪党参蘑菇煎对晚期食管癌胃癌化疗的免疫调节作用临床研究[J].时珍国医国药,2008,19(6):1474-1475
[17]杨晓慧,陈焕朝中西医结合治疗晚期胃癌临床观察[J].肿瘤防治研究,1999,26(6):426-427
[18]任立新,王亚红,哈敏文.华蟾素治疗晚期胃癌的临床疗效研究[J].中国中药杂志,2008,33(12):1474-1475
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[3] Casaretto L , Sousaand PLR, Mari JJ. Chemotherapy versus support cancer treatment in advanced gastric cancer: a meta-analysis. Brazilian J Med Bio Res, 2006,39:431-440
[4] Bang YJ,Kang WK,Kang YK et al.Docetaxel 75 mg/㎡ is active and well tolerated in patients with metastatic or recurrent gastric cancer:a phase II trial.Jpn J Clin Oncol 2002;32:248–254.
[5] Ohtsu A,Boku N,Tamura F et al.An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer.Am J Clin Oncol 1998;21:416–419.
[6] Sulkes A,Smyth J,Sessa C et al.Docetaxel (Taxotere) in advanced gastric cancer:results of a phase II clinical trial.EORTC Early Clinical Trials Group.Br J Cancer 1994;70:380–383.
[7] Ajani JA,Fairweather J,Dumas P et al.Phase II study of Taxol in patients with advanced gastric carcinomas.Cancer J Sci Am 1998;4:269–274.
[8] inzig AI,Neuberg D,Remick SC et al.Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy:the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293.Med Oncol 1996;13:87–93.
[9] Garcia AA,Leichman CG,Lenz HJ etal.Phase II trial of out patient schedule of paclitaxel in patients with previously untreated metastatic,measurable adeno- carcinoma of the stomach.Jpn J Clin Oncol 2001;31:275–278.
[10] Kim TW,Kang YK,Ahn JH et al.Phase II study of capecitabine plus cis-platin as first-line chemotherapy in advanced gastric cancer.Ann Oncol 2002;13:1893– 1898.
[11] Kollmannsberger C,Quietzsch D,Haag C et al.A phase II study of paclitaxel, weekly,24-hour continuous infusion 5-fluorouracil,folinic acid and cisplatin in patients with advanced gastric cancer.Br J Cancer 2000;83:458–462.
[12] Ryoo BY,Kim TW,Choi SJ et al.A phase II trial of paclitaxel (T) and carboplatin (C) for advanced gastric cancer refractory to 5-fluorouracil (F) and cisplatin/ heptaplatin (P).Proc Am Soc Clin Oncol 2001;20:128.
[13] Honecker F,Kollmannsberger C,Quietzsch D et al.Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil,folinic acid and 3-weekly cisplatin for the treatment of patients with advanced gastric cancer.Anticancer Drugs 2002;13:497–503.
[14] Gadgeel SM,Shields AF,Heilbrun LK et al.Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer.Am J Clin Oncol 2003; 26:37–41.
[15] Herrmann C, Jaeger D, Herrmann T. Second-line chemotherapy in advanced gastric cancer: A retrospective, single-center analysis. Journal of Calinical Oncology, 2007,25:15710.
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[17] LIM J,Cho J, Paik Y,et al. Survival benefit of sequential chemotherapy for advanced gastric cancer.2008 Gastrointestinal Cancers Symposium, Abstract No:67
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[25] Sym SJ, Ryu MH, Lee JL, et al. Salvage chemotherapy with biweekly irinotecan, plus5- fluorouracil and leucovorin in patients with advanced gastric cancer previously treated with fluoropyrimidine, platinum, and taxane. Am J Cin Oncol,2008,31:151-156.
[26] Baek JH, Kim JG, Sohn SK, et al. Biweekly irinotecan and cisplatin as second-line chemotherapy in pretreated patients with advanced gastric cancer: a multicenter phaseⅡstudy. J Korean Med Sci,2005,20:966-970.
[27] Suzuki S, Harada N, Takeo Y, et al. Bi- weekly irinotecan hydrochloride and cisplatin as a second-line chemotherapy for patients with advanced gastric cancer. Gan To Kagaku Ryoho,2007,34:2245-2248.
[28] Chun JH, Kim HK, Lee JS, et al. Weekly irinotecan in patients with metastatic gastric cancer failing cisplatin-based chemotherapy. Jpn J Clin Oncol,2004, 34:8-13.
[29] Catalano V, Graziano F, Salvagni S.. Lack of resistance to oxaliplatin(L-OHP)-based chemotherapy in patients (pts) with advanced gastric cancer previously treated with cisplatin-containing regimens:preliminary results of a phaseⅡstudy. Proc Am Soc Clin Oncol 21:2002(abstr 2200).
[30] Oh SC, Kim Y, Kim J, PhaseⅡtrial of oxalioplatin, 5-FU, and leucovorin chemotherapy for the previously treated pa-tients with advanced gastric cancer. Journal of Clinical Oncology,2007,25:15138s.
[31] Seo HY, Kim DS, Choi YS, et al. Treatment outcomes of oxaliplatin, 5-FU,and leucovorin as salvage therapy for pa-tients with advanced or metastatic gastric cancer: a retrospective analysis. Cancer Chemother Pharmacl, 2008 Apr
[32] Kim Y, Park S, Park J, et al. Oxaliplatin, 5-fluorouracil, and leuvocorin and (FOLFOX-4) combination chemo-therapy as salvage treatment in pretreated patients with advanced gastric cancer(AGC). J Clin Oncol,2008,26:1577s.
[33] Nagashima F,Boku N,Ohtsu A,et al.Biological Markers as a Predictor forResponse and Prognosisof Unresectable Gastric Cancer Patients Treated with Irinotecan and Cisplatin.Jpn J Clin Oncol,2005,35:714-719
[34] Wei J, Aou Z, Qian X. ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOL-FOX regimen.Br J Cancer, 2008, 98:1398-1402.
[35]金晶,李晔雄,局部进展期胃癌的综合治疗癌症进展杂志,2007,5:131-142.
[36] Macdonald JS,Smalley S,Benedetti J,et al.Postoperation conbination radiation and chemotherapy improves disease-free survival (DFS)and overall survival (OS) inresected adenocarcinoma of the stomach and G.E.junction .Results of intergroup study INT-0116 (SWOG 9008).Proc Am Soc Clin Oncol,2000, 19: 387-395.
[37] Kim S,Lim DH,Lee J,et al.An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach.Int-J-Radiat-Oncol-Biol-Phys,2005,63:1279-1285.
[38]李佩文.中药预防肿瘤转移的可能途径.第八届全国中西医结合肿瘤学术会议论文集(青岛),2000:171
[39]李锦毅。中药诱导细胞凋亡抗肿瘤转移治疗中的可能机制.辽宁中医杂志,1998(25~9):399
[40]李佩文主编。恶性肿瘤的术后治疗.人民卫生出版社.2002:l119
[41]王志学.中医药抗肿瘤转移治疗的思路与方法探讨.山东中医杂志.1997,16(12):532
[42]沈朝萍,刘锦霞,马兰花,等.浅谈活血化瘀中药抗肿瘤转移的思路与应用.国医论坛,2001,16(4):12
[43]李佩文.中药预防肿瘤转移的可能途径.中医杂志,1999,40(2):116
[44] [45]扬振江.活血化瘀对肿瘤转移影响的研究概况.湖南中医学院学报,2002,22(4):67
[46]王寅,潭侃,程明和等.中药防治肿瘤转移的研究进展.中草药, 2002,33(10).附3
[47]李忠主编.临床中医肿瘤学.第1版.辽宁科学技术出版社,2002:288~293
[48]扬新中.中医药防治肿瘤转移的思路。湖北中医药杂志,2002,24(8): 8
[49]李家庚,屈松柏主编.中医肿瘤防治大全.科学技术文献出版社,1994:584～588
[50]李佩文.恶性肿瘤的术后治疗.人民卫生出版社,2002:118
[51]王寅,潭侃,程明和,等.中药防治肿瘤转移的研究进展.中草药, 2002I 33(10).附3
[52]郑玉玲,韩新巍主编.中西医肿瘤诊疗大全.中国中医药出版社,1996:807
[53]王希胜,陈光伟,李仁廷,等.山仙颗粒抗肿瘤的临床与实验研究[J].陕西中医学院学报,2002,25(3):47—49.
[54]陈光伟.中医减轻恶性肿瘤放化疗毒副反应的作用[J].陕西中医学院学报,1999,22(5):56—57.
[55]金岚,金若敏.新编中药药理与临床应用[M].上海:上海科学技术文献出版社,1995.21:238,273,345,389.
[56]刘海金,蔡琦,曾祥福,艾迪注射液减轻胃肠癌化疗毒副作用的临床观察[J].赣南医学院学报,2002,25(1):86-87
[57]冷毓青,杨震玲,肖月升,等黄芪党参蘑菇煎对晚期食管癌胃癌化疗的免疫调节作用临床研究[J].时珍国医国药,2008,19(6):1474-1475
[58]杨晓慧陈焕朝中西医结合治疗晚期胃癌临床观察[J].肿瘤防治研究, 1999,26(6):426-427
[59]杨志新,尤建良中药微调3号辨证治疗晚期胃癌临床研究[J].辽宁中医杂志2006,33(11):1434-1435
[60]陈曦扶正消瘤汤治疗中晚期胃癌46例临床观察[J].航空航天医药,2008,19(2):99
[61]任立新,王亚红,哈敏文.华蟾素治疗晚期胃癌的临床疗效研究[J].中国中药杂志,2008,33(12):1474-1475
[62]宋洪恩.三参化瘀汤及拔毒攻坚散治疗胃癌93例.上海中医药杂志, 1997,(5):27.
[63]天伟.参芪注射液在胃癌化疗中的增效与减毒作用.北京中医药大学学报,1997,20(1):53.
[1] Yang L. Incidence and nortaliy of gastric cancer in China. World J Gastroenterol , 2006 , 12:17-20.
[2] Tsuchida Y,Therasse P.Response evaluation criteria in solid tumors (RECISq"): New guiddines J.Mc_d Pediatr Oncol,2001,37(1):1.
[3] Cancer Therapy Evaluation Program,Common Terminology Criteria for Adverse Events,Version 3.0,DCTD,NCI,NIH,DHHS.March 31,2003 (http://ctep.cancer. gov), Publish Date:August 9,2006
[4] Bang YJ,Kang WK,Kang YK et al.Docetaxel 75 mg/㎡ is active and well tolerated in patients with metastatic or recurrent gastric cancer:a phase II trial.Jpn J Clin Oncol 2002;32:248–254.
[5] Ohtsu A,Boku N,Tamura F et al.An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer.Am J Clin Oncol 1998;21:416–419.
[6] Sulkes A,Smyth J,Sessa C et al.Docetaxel (Taxotere) in advanced gastric cancer:results of a phase II clinical trial.EORTC Early Clinical Trials Group.Br J Cancer 1994;70:380–383.
[7] Ajani JA,Fairweather J,Dumas P et al.Phase II study of Taxol in patients with advanced gastric carcinomas.Cancer J Sci Am 1998;4:269–274.
[8] inzig AI,Neuberg D,Remick SC et al.Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy:the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293.Med Oncol 1996;13:87–93.
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