北京大学学报(医学版) ›› 2020, Vol. 52 ›› Issue (2): 261-268. doi: 10.19723/j.issn.1671-167X.2020.02.011

• 论著 • 上一篇    下一篇

肠内营养支持治疗减轻晚期食管癌患者化疗不良反应

孙志伟,贾军,杨颖,刘传玲,肖艳洁,余靖,张晓东   

  1. 北京大学肿瘤医院暨北京市肿瘤防治研究所消化系统肿瘤VIP-Ⅱ病区,恶性肿瘤发病机制及转化研究教育部重点实验室, 北京 100142
  • 收稿日期:2019-11-19 出版日期:2020-04-18 发布日期:2020-04-18
  • 通讯作者: 张晓东

Enteral nutrition support reduces toxicity of chemotherapy in patients with advanced or metastatic esophageal cancer

Zhi-wei SUN,Jun JIA,Ying YANG,Chuan-ling LIU,Yan-jie XIAO,Jing YU,Xiao-dong ZHANG   

  1. VIP-Ⅱ Gastrointestinal Cancer Division of the Department of Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
  • Received:2019-11-19 Online:2020-04-18 Published:2020-04-18
  • Contact: Xiao-dong ZHANG

RICH HTML

  

摘要:

目的 评估肠内营养支持治疗对晚期食管癌患者一线化疗疗效及不良反应的影响.方法: 回顾性收集2014年7月至2016年12月于北京大学肿瘤医院接受一线化疗的118例不可手术切除的局部进展期或转移性食管癌患者资料,将患者分为两组,营养支持组(化疗同时予肠内营养支持)和对照组(单纯化疗).比较两组患者化疗前后各营养指标[KPS功能状态评分(Karnofsky performance status),体质量,体重指数(body mass index,BMI),血红蛋白,淋巴细胞数,总蛋白,白蛋白,甘油三酯,总胆固醇]的变化及化疗疗效,化疗不良反应的差异.结果: (1)对照组化疗后,患者体质量,BMI和血红蛋白水平均明显下降(P<0.001);营养支持组患者化疗后,患者体质量和BMI并无明显变化,仅血红蛋白有明显下降;两组患者化疗前后其他营养指标差异均无统计学意义.(2)与对照组相比,营养支持组化疗后3级以上血液学毒性发生率显著降低(15.4% vs. 42.1%,P=0.004),3级以上非血液学毒性发生率也有所降低但两组差异无统计学意义(0 vs. 9.2%,P=0.123).Logistic回归多因素分析显示,营养治疗是食管癌患者化疗后发生3级以上血液学毒性的独立影响因素(P=0.008,RR=6.048,95%CI:1.589~23.027).(3)两组患者化疗疗效差异无统计学意义.结论: 晚期食管癌患者在化疗同时予肠内营养支持治疗可改善患者营养状态,减轻化疗毒性和不良反应.

关键词: 食管肿瘤, 化疗, 肠内营养支持

Abstract:

Objective: To assess the impact of enteral nutrition support on response and toxicity of the first-line chemotherapy in those patients with advanced or metastatic esophageal cancer.Methods: We collected the clinical data of 118 patients with unresectable advanced or metastatic esophageal cancer who received the first-line chemotherapy in our center from July 2014 to December 2016. All these 118 eso-phageal cancer patients were then divided into two groups: the nutrition group (received enteral nutrition support in addition to chemotherapy) and the control group (received chemotherapy only). Differences were analyzed before and after chemotherapy in each of the nutritional indicators including Karnofsky performance status (KPS), weight, body mass index (BMI), hemoglobin (Hb), number of lymphocytes (Lymph), total protein (TP), albumin (Alb), triglycerides (TG), total cholesterol (TC) in both groups. And differences of the efficacy and toxicities of the first-line chemotherapy between the two groups were also analyzed.Results: (1) Weight, BMI and Hb were all significantly decreased after chemotherapy in the control group (P<0.001), while there was no significant change of weight and BMI in the nutrition group, just with Hb decrease only. However, there was no significant change of all the other nutrition indicators after chemotherapy in both groups. (2) Compared with the control group, the nutrition group had significantly lower incidence of grade 3 to 4 hematologic toxicities after chemotherapy (15.4% vs. 42.1%, P=0.004). In addition, the incidence of grade 3 to 4 nonhematologic toxicities after chemotherapy was also lower in the nutrition group but without statistical significance (0 vs. 9.2%, P=0.123). Logistic regression model was then used for multivariate analysis to identify the factors that affected the toxicity of chemotherapy in these patients, and the results showed that nutrition therapy was an independent influencing factor of grade 3 or higher hematological toxicity after chemotherapy in the patients with esophageal cancer (P=0.008, RR=6.048, 95%CI: 1.589-23.027). (3) The response rate of chemotherapy between the control group and the nutrition group had not significant difference.Conclusion: Enteral nutrition support in addition to chemotherapy could improve nutrition status and reduce toxicity of chemotherapy in advanced or metastatic esophageal cancer patients.

Key words: Esophageal neoplasms, Chemotherapy, Enteral nutrition support

中图分类号: 

  • R735.1

表1

患者一般资料"

Items Control group, n (%) Nutrition group, n (%) P value
Gender 0.084
Male 60 (76.9) 36 (90.0)
Female 18 (23.1) 4 (10.0)
Age/years 0.824
≤70 73 (93.6) 37 (92.5)
>70 5 (6.4) 3 (7.5)
KPS 0.438
≥90 73 (93.6) 35 (87.5)
80-70 5 (6.4) 5 (12.5)
Grade 0.888
Well 51 (65.4) 24 (60.0)
Poorly 24 (30.8) 12 (30.0)
Not known 3 (3.8) 4 (10.0)
Stage 0.147
Locally advanced 57 (73.1) 24 (60.0)
Recurrent/metastatic 21 (26.9) 16 (40.0)

表2

化疗前营养指标"

Items Control group, $\bar{x}±s$ Nutrition group, $\bar{x}±s$ P value
KPS 89.49±2.74 88.75±3.35 0.234
BMI/(kg/m2) 22.65±3.81 20.64±2.73 0.004
Hb/(g/L) 141.65±14.26 130.31±25.86 0.003
Lymph/(×109/L) 1.82±0.68 1.63±0.47 0.104
TP/(g/L) 70.24±4.47 69.57±6.77 0.577
Alb/(g/L) 43.11±3.13 41.47±7.64 0.200
TG/(mmol/L) 1.12±0.50 1.17±0.88 0.693
TC/(mmol/L) 4.93±1.10 4.74±1.04 0.394

表3

全部食管癌患者化疗前后营养指标变化($\bar{x}±s$)"

表4

局部进展期食管癌患者化疗前后营养指标变化($\bar{x}±s$)"

表5

复发/转移性食管癌患者化疗前后营养指标变化($\bar{x}$ ±s)"

Items KPS Weight/kg BMI/(kg/m2) Hb/(g/L)
Nutrition group
B 88.75±3.42 58.70±8.95 21.01±2.36 135.12±11.93
A 89.38±2.50 57.49±9.64 20.56±2.58 123.81±9.37
Δ(B-A) -0.63±2.50 1.21±2.77 0.45±1.05 11.31±14.46
P 0.333 0.112 0.119 0.007
Control group
B 89.05±3.01 64.11±10.37 22.82±2.52 139.84±15.67
A 88.10±4.02 62.60±10.54 22.29±2.74 124.11±14.89
Δ(B-A) 0.95±3.01 1.51±1.89 0.53±0.70 15.74±11.74
P 0.160 0.003 0.004 <0.001
Items Lymph/(×109/L) TP/(g/L) Alb/(g/L) TG/(mmol/L) TC/(mmol/L)
Nutrition group
B 1.69±0.50 71.30±5.63 42.65±3.38 1.04±0.35 4.79±1.11
A 1.55±0.51 72.46±3.88 42.49±4.12 1.23±0.71 4.73±1.67
Δ(B-A) 0.14±0.35 -1.16±5.53 0.16±5.37 -0.19±0.63 0.07±1.70
P 0.134 0.417 0.909 0.237 0.874
Control group
B 1.63±0.65 71.18±4.15 43.33±2.59 1.05±0.39 4.82±1.24
A 1.55±0.61 69.89±3.07 42.56±3.10 1.21±0.47 4.62±1.10
Δ(B-A) 0.08±0.56 1.29±4.20 0.78±2.66 -0.17±0.39 0.20±0.61
P 0.539 0.208 0.231 0.093 0.191

表6

食管癌患者化疗疗效与肠内营养相关性"

Stage Efficacy Control group Nutrition group P value
All Response rate 43.7% 41.7% 0.844
Disease control rate 95.8% 100.0% 0.528
Locally advanced Response rate 41.5% 27.3% 0.246
Disease control rate 96.2% 100.0% 1.000
Recurrent/metastatic Response rate 50.0% 64.3% 0.490
Disease control rate 94.4% 100.0% 1.000

表7

食管癌患者化疗不良反应与肠内营养的相关性"

Stage Efficacy Control group Nutrition group P value
All Response rate 43.7% 41.7% 0.844
Disease control rate 95.8% 100.0% 0.528
Locally advanced Response rate 41.5% 27.3% 0.246
Disease control rate 96.2% 100.0% 1.000
Recurrent/metastatic Response rate 50.0% 64.3% 0.490
Disease control rate 94.4% 100.0% 1.000

表8

食管癌患者化疗不良反应相关因子的Logistic回归多因素分析"

Variables Wald OR 95%CI P
Gender 0.227 0.705 0.167-2.976 0.634
Age 0.335 0.558 0.077-4.026 0.563
KPS 1.862 5.174 0.488-54.851 0.172
Grade 0.238 0.755 0.244-2.335 0.626
Stage 0.066 1.163 0.368-3.678 0.797
BMI 0.910 1.074 0.927-1.245 0.340
Hb 2.435 0.966 0.924-1.009 0.119
Lymph 0.175 1.192 0.524-2.712 0.675
TP 0.735 1.064 0.923-1.227 0.391
Alb 1.551 1.150 0.923-1.434 0.213
TG 0.846 0.589 0.191-1.820 0.358
TC 0.046 1.063 0.607-1.863 0.831
Nutrition support 6.962 6.048 1.589-23.027 0.008
[1] 于振涛 . 食管癌围手术期营养治疗[J]. 肿瘤代谢与营养电子杂志, 2015,2(2):19-22.
[2] Bozzetti F, Mariani L, Lo VS , et al. The nutritional risk in onco-logy: a study of 1,453 cancer outpatients[J]. Support Care Cancer, 2012,20(8):1919-1928.
[3] Cong MH, Li SL, Cheng GW , et al. An interdisciplinary nutrition support team improves clinical and hospitalized outcomes of esophageal cancer patients with concurrent chemoradiotherapy[J]. Chin Med J (Engl), 2015,128(22):3003-3007.
[4] Wu W, Zhong M, Zhu DM , et al. Effect of early full-calorie nutrition support following esophagectomy: a randomized controlled trial[J]. JPEN J Parenter Enteral Nutr, 2017,41(7):1146-1154.
[5] Takesue T, Takeuchi H, Ogura M , et al. A prospective rando-mized trial of enteral nutrition after thoracoscopic esophagectomy for esophageal cancer[J]. Ann Surg Oncol, 2015,22(3):S802-809.
[6] Peng J, Cai J, Niu ZX , et al. Early enteral nutrition compared with parenteral nutrition for esophageal cancer patients after esophagectomy: a meta-analysis[J]. Dis Esophagus, 2016,29(4):333-341.
[7] Moro K, Koyama Y, Kosugi SI , et al. Low fat-containing elemental formula is effective for postoperative recovery and potentially useful for preventing chyle leak during postoperative early enteral nutrition after esophagectomy[J]. Clin Nutr, 2016,35(6):1423-1428.
[8] Odelli C, Burgess D, Bateman L , et al. Nutrition support improves patient outcomes, treatment tolerance and admission characteristics in oesophageal cancer[J]. Clin Oncol (R Coll Radiol), 2005,17(8):639-645.
[9] 吕家华, 李涛, 谢丛华 , 等. 食管癌放疗患者肠内营养专家共识[J]. 肿瘤代谢与营养电子杂志, 2015,2(4):29-32.
[10] Arends J, Bachmann P, Baracos V , et al. ESPEN guidelines on nutrition in cancer patients[J]. Clin Nutr, 2017,36(1):11-48.
[11] Nicolini A, Ferrari P, Masoni MC , et al. Malnutrition, anorexia and cachexia in cancer patients: A mini-review on pathogenesis and treatment[J]. Biomed Pharmacother, 2013,67(8):807-817.
[12] Zhang XL, Xu L, Shen JM , et al. Metabolic signatures of esophageal cancer: NMR-based metabolomics and UHPLC-based focused metabolomics of blood serum[J]. Biochim Biophys Acta, 2013,1832(8):1207-1216.
[13] Trachootham D, Songkaew W, Hongsachum B , et al. Nutri-jelly may improve quality of life and decrease tube feeding demand in head and neck cancer patients[J]. Support Care Cancer, 2015,23(5):1421-1430.
[14] Martin RC, Cannon RM, Brown RE , et al. Evaluation of quality of life following placement of self-expanding plastic stents as a bridge to surgery in patients receiving neoadjuvant therapy for esophageal cancer[J]. Oncologist, 2014,19(3):259-265.
[15] Andreyev HJ, Norman AR, Oates J , et al. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?[J]. Eur J Cancer, 1998,34(4):503-509.
[16] Chau I, Norman AR, Cunningham D , et al. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer-pooled analysis from three multicenter, randomized, controlled trials using individual patient data[J]. J Clin Oncol, 2004,22(12):2395-2403.
[17] Crumley AB ,McMillan DC, McKernan M, et al. Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-esophageal cancer[J]. Br J Cancer, 2006,94(5):637-641.
[18] Lecleire S, Di Fiore F, Antonietti M , et al. Undernutrition is predictive of early mortality after palliative self-expanding metal stent insertion in patients with inoperable or recurrent esophageal cancer[J]. Gastrointest Endosc, 2006,64(4):479-484.
[19] Miyata H, Yano M, Yasuda T , et al. Randomized study of clinical effect of enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esopha-geal cancer[J]. Clin Nutr, 2012,31(3):330-336.
[20] Miyata H, Yano M, Yasuda T , et al. Randomized study of the clinical effects ω-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer[J]. Nutrition, 2017,33:204-210.
[21] Enzinger PC, Ilson DH, Kelsen DP . Chemotherapy in esophageal cancer[J]. Semin Oncol, 1999,26(5):12-20.
[22] Bleiberg H, Conroy T, Lacave AJ , et al. Randomised phase Ⅱ study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer[J]. Eur J Cancer, 1997,33(8):1216-1220.
[23] Huang J, Zhou Y, Zhang H , et al. A phase Ⅱ study of biweekly paclitaxel and cisplatin chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma: ERCC1 expression predicts response to chemotherapy[J]. Med Oncol, 2013,30(1):343.
[24] Lu M, Wang X, Shen L , et al. Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: A single centre prospective phase Ⅱ trial[J]. Cancer Sci, 2016,107(4):486-490.
[1] 刘京,陆爱东,左英熹,吴珺,黄志卓,贾月萍,丁明明,张乐萍,秦炯. 儿童急性淋巴细胞白血病合并癫痫发作75例临床特征和预后分析[J]. 北京大学学报(医学版), 2022, 54(5): 948-953.
[2] 耿良,吕静,范敬. 肺瘤平膏联合环磷酰胺化疗对肺癌的抑瘤作用和酸性微环境的影响[J]. 北京大学学报(医学版), 2020, 52(2): 247-253.
[3] 马义祥,刘敬伟,齐康,张继新,林钢,刘海波,商学谦,李简. 原发性纵隔卵黄囊瘤7例[J]. 北京大学学报(医学版), 2019, 51(6): 1091-1095.
[4] 徐稼轩,王宏志,董军,陈小杰,杨勇,陈仁雄,王国栋. 食管癌术后急性肺损伤/急性呼吸窘迫综合征的危险因素分析[J]. 北京大学学报(医学版), 2018, 50(6): 1057-1062.
[5] 陈杨,王艳荣,石燕,戴广海. 晚期结直肠癌患者一线应用FOLFOX方案化疗引起中性粒细胞减少的预后价值[J]. 北京大学学报(医学版), 2017, 49(4): 669-674.
[6] 瓦斯里江·瓦哈甫, 何志嵩, 周利群. 成人肾母细胞瘤一例[J]. 北京大学学报(医学版), 2008, 40(3): 334-338.
[7] 熊小平. 镍钛合金覆膜支架治疗食管恶性狭窄[J]. 北京大学学报(医学版), 2008, 40(2): 205-207.
[8] 吴楠, 杨跃. 保留胸肌的微创剖胸切口在早期食管胸中上段癌手术中的应用[J]. 北京大学学报(医学版), 2006, 38(6): 640-643.
[9] Guo-hui LU. 治疗相关的急性髓系白血病的临床细胞遗传学诊断[J]. 北京大学学报(医学版), 2005, 37(1): 10-13.
[10] 马丽萍, 潘秀英, 李娜, 刘玉京, 陈晓欣. gp96多肽复合物介导的细胞毒性T淋巴细胞对食管腺癌细胞的免疫杀伤作用[J]. 北京大学学报(医学版), 2004, 36(5): 525-528.
[11] 张春风, 曹邦伟, 陆哲明, 邢海平, 崔建国, 宁涛, 柯杨. 中国安阳地区人群IRF-3基因Codon427位点多态性与食管癌的关联性研究[J]. 北京大学学报(医学版), 2004, 36(4): 345-347.
[12] 管宏, 赵慧云, 沈磊, 李五岭, 王建华, 王春荣, 徐福. 联合应用重组TPO和G-CSF对骨髓抑制性小鼠外周血小板及白细胞恢复的影响[J]. 北京大学学报(医学版), 2001, 33(2): 181-182.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!