胃癌根治术后静脉联合腹腔热灌注辅助化疗的临床疗效观察
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摘要
目的探讨进展期胃癌D2淋巴结根治术后患者行静脉联合腹腔内热灌注辅助化疗的临床疗效。方法选取139例进展期胃癌D2淋巴结根治术后患者,按随机数字表法分为试验组与对照组。试验组69例化疗方案:多西他赛75 mg/m~2,静脉滴注1 h,d1;奥沙利铂130 mg/m~2,静脉滴注3 h,d1;氟尿嘧啶2 500 mg/m~2,加入0.9%氯化钠2 000 mL,加热至45℃后匀速灌入腹腔;21 d为1个周期。对照组70例化疗方案:多西他赛75 mg/m~2,静脉滴注1 h,d1;奥沙利铂130 mg/m~2,静脉滴注3 h,d1;氟尿嘧啶500 mg/m~2,持续静脉滴注d1～d5;21 d为1个周期。随访5～8年,观察两组不良反应、转移复发情况及生存情况。结果两组患者不良反应发生率比较,差异均无统计学意义(均P>0.05)。试验组与对照组复发转移率为37.7%(29/69)和60.0%(42/70),差异具有统计学意义(P=0.034),其中腹膜转移率为11.6%(8/69)和25.7%(18/70),差异具有统计学意义(P=0.033);复发率及其他部位转移率比较,差异均无统计学意义(均P>0.05)。试验组和对照组术后1、3和5年无瘤生存率(disease-free survival,DFS)分别为95.6%、65.2%、57.9%和94.3%、48.6%、40.0%;两组整体DFS比较,差异具有统计学意义(P=0.031)。试验组和对照组术后1、3和5年总生存率(overall survival,OS)分别为100.0%、81.1%、60.9%和100.0%、62.8%、42.9%;两组整体OS比较,差异具有统计学意义(P=0.025)。结论进展期胃癌D2淋巴结根治术后患者行静脉联合腹腔热灌注辅助化疗安全、有效,能降低转移率,提高远期生存率。
Objective To evaluate the efficacy of adjuvant intravenous chemotherapy combined with intraperitoneal hyperthermic chemotherapy in treatment of advanced gastric cancer patients after radical gastrectomy. Methods One-hundred-and-thirty-nine patients with advanced gastric cancer after D2 lymph node radical gastrectomy were randomly assigned into two groups. Both groups received docetaxel combined with oxalipatin adjuvant chemotherapy with 21 d as one cycle(75 mg/m~2 docetaxel, i.v gtt 1 h,d1; 130 mg/m~2 oxalipatin, i.v gtt 3 h, d1). The study group(n=69) was given additional intraperitoneal hyperthermic chemotherapy(5-fluorouracil 2 500 mg/m~2 was added into 2 000 mL 0.9% NaCl solution, heated to 45℃ and administered by intraperitoneal perfusion); while the control group(n=70) was given intravenous 5-fluorouracil treatment(500 mg/m~2 5-fluorouracil, i.v gtt 24 h,d1-d5). The patients were followed up for 5 to 8 years, and the adverse events, metastasis rate, relapse status and survival rate were documented and compared between two groups. Results No significant difference was observed for the incidence of adverse events between the two groups(P>0.05). The recurrence/metastasis rates were 37.7%(29/69)and 60.0%(42/70) in the study group and the control group(P=0.034), respectively. Moreover, the peritoneal metastasis were 11.6%(8/69) and 25.7%(18/70) in the two groups(P=0.033), whereas the metastasis rate of other body regions was not significantly different(all P>0.05). The 1-, 3-and 5-year disease-free survival(DFS) rates in the study group were significantly higher than those in the control group(95.6%, 65.2% and 57.9% vs 94.3%, 48.6% and 40.0%, P=0.031). The 1-, 3-and 5-year overall survival rates of the study group were also higher than those of the control group(100.0%, 81.1% and 60.9% vs 100.0%, 62.8% and 42.9%, P=0.025). Conclusion For advanced gastric cancer patients with radical gastrectomy, the adjuvant intravenous chemotherapy combined with intraperitoneal hyperthermic chemotherapy is safe and effective, which can increase survival rate and decrease metastasis rate.
Objective To evaluate the efficacy of adjuvant intravenous chemotherapy combined with intraperitoneal hyperthermic chemotherapy in treatment of advanced gastric cancer patients after radical gastrectomy. Methods One-hundred-and-thirty-nine patients with advanced gastric cancer after D2 lymph node radical gastrectomy were randomly assigned into two groups. Both groups received docetaxel combined with oxalipatin adjuvant chemotherapy with 21 d as one cycle(75 mg/m~2 docetaxel, i.v gtt 1 h,d1; 130 mg/m~2 oxalipatin, i.v gtt 3 h, d1). The study group(n=69) was given additional intraperitoneal hyperthermic chemotherapy(5-fluorouracil 2 500 mg/m~2 was added into 2 000 mL 0.9% NaCl solution, heated to 45℃ and administered by intraperitoneal perfusion); while the control group(n=70) was given intravenous 5-fluorouracil treatment(500 mg/m~2 5-fluorouracil, i.v gtt 24 h,d1-d5). The patients were followed up for 5 to 8 years, and the adverse events, metastasis rate, relapse status and survival rate were documented and compared between two groups. Results No significant difference was observed for the incidence of adverse events between the two groups(P>0.05). The recurrence/metastasis rates were 37.7%(29/69)and 60.0%(42/70) in the study group and the control group(P=0.034), respectively. Moreover, the peritoneal metastasis were 11.6%(8/69) and 25.7%(18/70) in the two groups(P=0.033), whereas the metastasis rate of other body regions was not significantly different(all P>0.05). The 1-, 3-and 5-year disease-free survival(DFS) rates in the study group were significantly higher than those in the control group(95.6%, 65.2% and 57.9% vs 94.3%, 48.6% and 40.0%, P=0.031). The 1-, 3-and 5-year overall survival rates of the study group were also higher than those of the control group(100.0%, 81.1% and 60.9% vs 100.0%, 62.8% and 42.9%, P=0.025). Conclusion For advanced gastric cancer patients with radical gastrectomy, the adjuvant intravenous chemotherapy combined with intraperitoneal hyperthermic chemotherapy is safe and effective, which can increase survival rate and decrease metastasis rate.
引文
[1] 韩光锋.晚期胃癌的内科治疗现状和进展[J].实用肿瘤杂志,2017,32(6):569-574.
[2] Fidler IJ.The pathogenesis of cancer metastasis:the "seed and soil" hypothesis revisited[J].Nat Rev Cancer,2003,3(6):453-458.
[3] 朱志,王振宁.胃癌腹膜转移的诊治研究进展[J].实用肿瘤杂志,2018,33(3):204-208.
[4] Polom K,Marano L,Roviello G,et al.Evolution and emerging future of cytoreducxtive surgery and hyperthermic intraperitoneal chemoperfusion in gastric cancer:From treating the incurable to preventing recurrence[J].Int J Hyperthermia,2016,32(2):173-179.
[5] Seshadri RA,Glehen O.Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer[J].World J Gastroenterol,2016,22(3):1114-1130.
[6] Koga S,Hamazoc R,Macta M,et al.Prophaylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal with mitomycin[J].Cancer,1988,61(2):232-237.
[7] Kodera Y,Takahashi N,Yoshikawa T,et al.Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer:a preliminary safety analysis of the INPACT study,a randomized controlled trial[J].Gastric Cancer,2017,20(1):190-199.
[8] Washington K.7th edition of the AJCC cancer staging manual:stomach[J].Ann Surg Oncol,2010,17(12):3077-3079.
[9] Akazawa S,Yamashina T,Konuma Y,et al.Management of anticancer drug adverse reactions[J].Nihon Rinsho,2001,59(Suppl 4):409-414.
[10] Sasako M,Sakuramoto S,Katai H,et al.Five-year outcomes of a randomized phase Ⅲ trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage Ⅱ or Ⅲ gastric cancer[J].J Clin Oncol,2011,29(33):4387-4393.
[11] Yonemura Y,Bandou E,Kawamura T,et al.Quantitative prognostic indicators of peritoneal dissemination of gastric cancer[J].Eur J Surg oncol,2006,32(6):602-606.
[12] Braam HJ,Schellens JH,Boot H,et al.Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer[J].Crit Rev Oncol Hematol,2015,95(3):282-296.
[13] Wu X,Li Z,Li Z,et al.Hyperthermic intraperitoneal chemotherapy plus simultaneous versus staged cytoreductive surgery for gastric cancer with occult peritoneal metastasis[J].J Surg Oncol,2015,111(7):840-847.
[14] Sheshadri DB,Chakravarthy MR.Anaesthetic considerations in the perioperative management of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J].Indian J Surg Oncol,2016,7(2):236-243.
[15] 姬忠贺,孙建华,武海涛,等.腹腔热灌注化疗对腹腔游离癌细胞杀灭效果的评价[J].中国肿瘤临床,2015,42(19):963-968.
[16] 林爱德,孙怀玉,曲牟文,等.大容积加温低渗5-Fu腹腔化疗预防胃癌术后复发和肝转移的药代动力学研究[J].癌症,2002,21(4):424-429.
[17] 詹宏杰,梁寒,王宝贵,等.60例进展期胃癌术中腹腔热灌化疗的临床观察[J].中国肿瘤临床,2010,37(4):229-232.
[18] 郭明浩.腹腔镜胃癌 D2 根治术联合腹腔内热灌注化疗治疗胃癌的疗效研[J].腹腔镜外科杂志,2017,22(1):42-45.
[19] 腹腔热灌注化疗技术临床应用专家协作组.腹腔热灌注化疗技术临床应用专家共识(2016版)[J].中华胃肠外科杂志,2016,19(2):121-125.
[2] Fidler IJ.The pathogenesis of cancer metastasis:the "seed and soil" hypothesis revisited[J].Nat Rev Cancer,2003,3(6):453-458.
[3] 朱志,王振宁.胃癌腹膜转移的诊治研究进展[J].实用肿瘤杂志,2018,33(3):204-208.
[4] Polom K,Marano L,Roviello G,et al.Evolution and emerging future of cytoreducxtive surgery and hyperthermic intraperitoneal chemoperfusion in gastric cancer:From treating the incurable to preventing recurrence[J].Int J Hyperthermia,2016,32(2):173-179.
[5] Seshadri RA,Glehen O.Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer[J].World J Gastroenterol,2016,22(3):1114-1130.
[6] Koga S,Hamazoc R,Macta M,et al.Prophaylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal with mitomycin[J].Cancer,1988,61(2):232-237.
[7] Kodera Y,Takahashi N,Yoshikawa T,et al.Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer:a preliminary safety analysis of the INPACT study,a randomized controlled trial[J].Gastric Cancer,2017,20(1):190-199.
[8] Washington K.7th edition of the AJCC cancer staging manual:stomach[J].Ann Surg Oncol,2010,17(12):3077-3079.
[9] Akazawa S,Yamashina T,Konuma Y,et al.Management of anticancer drug adverse reactions[J].Nihon Rinsho,2001,59(Suppl 4):409-414.
[10] Sasako M,Sakuramoto S,Katai H,et al.Five-year outcomes of a randomized phase Ⅲ trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage Ⅱ or Ⅲ gastric cancer[J].J Clin Oncol,2011,29(33):4387-4393.
[11] Yonemura Y,Bandou E,Kawamura T,et al.Quantitative prognostic indicators of peritoneal dissemination of gastric cancer[J].Eur J Surg oncol,2006,32(6):602-606.
[12] Braam HJ,Schellens JH,Boot H,et al.Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer[J].Crit Rev Oncol Hematol,2015,95(3):282-296.
[13] Wu X,Li Z,Li Z,et al.Hyperthermic intraperitoneal chemotherapy plus simultaneous versus staged cytoreductive surgery for gastric cancer with occult peritoneal metastasis[J].J Surg Oncol,2015,111(7):840-847.
[14] Sheshadri DB,Chakravarthy MR.Anaesthetic considerations in the perioperative management of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J].Indian J Surg Oncol,2016,7(2):236-243.
[15] 姬忠贺,孙建华,武海涛,等.腹腔热灌注化疗对腹腔游离癌细胞杀灭效果的评价[J].中国肿瘤临床,2015,42(19):963-968.
[16] 林爱德,孙怀玉,曲牟文,等.大容积加温低渗5-Fu腹腔化疗预防胃癌术后复发和肝转移的药代动力学研究[J].癌症,2002,21(4):424-429.
[17] 詹宏杰,梁寒,王宝贵,等.60例进展期胃癌术中腹腔热灌化疗的临床观察[J].中国肿瘤临床,2010,37(4):229-232.
[18] 郭明浩.腹腔镜胃癌 D2 根治术联合腹腔内热灌注化疗治疗胃癌的疗效研[J].腹腔镜外科杂志,2017,22(1):42-45.
[19] 腹腔热灌注化疗技术临床应用专家协作组.腹腔热灌注化疗技术临床应用专家共识(2016版)[J].中华胃肠外科杂志,2016,19(2):121-125.