切换至 "中华医学电子期刊资源库"
高级检索
中华结直肠疾病电子杂志

中华结直肠疾病电子杂志 ›› 2018, Vol. 07 ›› Issue (05) : 420 -430. doi: 10.3877/cma.j.issn.2095-3224.2018.05.004

所属专题： 文献；

青年专家论坛

伴有合并症的结直肠癌治疗的药物选择
房文通1, 顾艳宏2,†()   
  1. 1. 210029　南京医科大学第一附属医院药学部
    2. 210029　南京医科大学第一附属医院肿瘤科
  • 收稿日期:2017-07-27 出版日期:2018-10-25
  • 通信作者: 顾艳宏
  • 基金资助:
    江苏省药学会Shire生物药学基金(No.S201602); 促进海峡两岸科技合作联合基金(No.U1505229)

Medication options for colorectal cancer with complications

Wentong Fang1, Yanhong Gu2,†()   

  1. 1. Department of Pharmacy, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
    2. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • Received:2017-07-27 Published:2018-10-25
  • Corresponding author: Yanhong Gu
  • About author:
    Corresponding author: Gu Yanhong, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

房文通, 顾艳宏. 伴有合并症的结直肠癌治疗的药物选择[J]. 中华结直肠疾病电子杂志, 2018, 07(05): 420-430.

Wentong Fang, Yanhong Gu. Medication options for colorectal cancer with complications[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2018, 07(05): 420-430.

结直肠癌是我国及世界范围内最常见的肿瘤之一，结直肠癌合并特殊功能状态或疾病如肝肾功能不全、肝炎、心血管疾病、老年、体弱等的患者并不少见。合并特殊功能状态或疾病的结直肠癌患者的治疗，既要考虑伴随疾病对结直肠癌治疗选择的影响，又要考虑结直肠癌治疗对既有疾病的影响。本文将主要从伴随疾病对结直肠癌治疗药物药动学和药效学的影响方面，系统回顾现有资料，探讨伴有合并症的结直肠癌的治疗选择。

关键词: 结直肠肿瘤, 肾功能不全, 肝功能不全, 心脏毒性, 老年患者

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in China and worldwide. CRC accompany with other system diseases or insufficiency, such as kidney insufficiency, liver insufficiency, hepatitis, cardiovascular disease, agedness or weakness is not uncommon. Complications may affect the treatment choices of CRC, while CRC therapies also have an effect the complications. We overviewed the effect of complications on pharmacokinetics and pharmacodynamics of drug therapy, and discussed the optimal medication for these patients.

Key words: Colorectal neoplasms, Renal insufficiency, Liver insufficiency, Cardiac toxicity, Elderly patients
表1 不同肾功能状态时卡培他滨及其代谢产物的药动学参数
Ccr 组I 组II 组III 组IV
>80 mL/min 51~80 mL/min 30~50 mL/min <30 mL/min
检测时间 第1天（n=6） 第14天（n=6） 第1天（n=8） 第14天（n=7） 第1天（n=6） 第14天（n=6） 第1天（n=4） 第14天（n=2）
卡培他滨 ? ? ? ? ? ? ? ?
Cmax（μg/mL） 4.63 5.05 3.47 3.80 4.10 3.32 5.07 2.25/2.61
tmax（h） 1.00 1.50 2.03 1.00 2.51 2.00 1.23 2.00/0.48
AUC0-∞（μg.h/mL） 5.95 6.46 5.40 6.13 6.73 7.23 7.06 3.88/3.98
t1/2（h） 0.56 0.37 0.46 0.48 0.48 0.56 0.50 0.50/0.58
5′-DFCR ? ? ? ? ? ? ? ?
Cmax（μg/mL） 5.20 6.26 5.15 5.38 4.65 2.71 6.23 3.37/3.95
tmax（h） 1.03 1.51 2.03 1.07 2.51 2.13 1.54 3.00/1.02
AUC0-∞（μg.h/mL） 11.00 11.40 12.20 12.00 11.40 7.26 11.90 7.40/9.74
t1/2（h） 0.79 0.72 0.80 0.78 0.71 0.74 0.83 0.59/0.92
5′-DFUR ? ? ? ? ? ? ? ?
Cmax（μg/mL） 6.55 11.20 6.22 7.91 7.74 9.02 12.50 12.3/9.79
tmax（h） 1.03 1.51 2.05 2.00 2.98 2.63 1.54 3.00/1.02
AUC0-∞（μg.h/mL） 13.50 18.80 13.40 15.40 18.20 23.20 23.00 22.5/22.7
t1/2（h） 0.72 0.56 0.61 0.58 0.62 0.67 0.68 0.54/0.70
5-FU ? ? ? ? ? ? ? ?
Cmax（μg/mL） 0.42 0.96 0.26 0.58 0.31 0.47 0.54 0.754/0.390
tmax（h） 1.03 1.51 2.03 1.07 2.98 2.63 1.54 3.00/1.02
AUC0-∞（μg.h/mL） 0.80 1.53 0.55 1.09 0.72 1.18 1.01 1.456/0.966
t1/2（h） 0.78 0.60 0.64 0.69 0.65 0.75 0.71 0.58/0.72
FBAL ? ? ? ? ? ? ? ?
Cmax（μg/mL） 7.34 6.55 6.39 7.80 7.76 8.93 11.20 19.6/17.1
tmax（h） 2.57 3.00 3.00 2.00 5.01 4.02 3.50 5.00/3.12
AUC0-∞（μg.h/mL） 37.50 36.50 35.20 44.80 69.50 63.90 133.00 163/NC
t1/2（h） 3.07 3.88 3.38 3.25 4.42 5.45 7.29 8.85/NC
表2 不同肾功能状态时奥沙利铂的药动学参数
Ccr 组I 组II 组III 组IV
≥60 mL/min 40~59 mL/min 20~39 mL/min <20 mL/min
剂量（患者数） 130 mg/m2（n=11） 105 mg/m2（n=3） 130 mg/m2（n=6） 80 mg/m2（n=1） 105 mg/m2（n=2） 130 mg/m2（n=5） 60 mg/m2（n=1）
Cmax（μg/mL） 1.31 0.84 1.31 0.63 1.45 1.39 0.72
AUC0-∞（μg.h/mL） 16.40 32.70 39.70 29.50 42 44.60 32.20
Vss，L/m2 361 224 136 100 99 144 135
CL（L/h/m2） 4.20 1.80 1.74 1.33 1.22 1.61 0.91
0~24小时尿排泄量（%） 36.60 19.90 24.20 18.10 15.60 19 7.13
表3 个案报道中HD患者应用奥沙利铂的药动学参数
? Katsumata等，2008[11] Watayo等，2010[12] Horimatsu等，2011[13] Gori S等，2014[14]
性别 男性 男性 男性 男性
年龄（y） 65 58 50 55
治疗方案 mFOLFOX6 mFOLFOX6 mFOLFOX6 FLOX
剂量（mg/m2） 40 40~50 60~85 42.5
总剂量（mg） 68 68~85 — 85
透析开始时间 用药后30 min 用药后立即 用药后立即 用药后1.5 h
透析时间（h） 3 4 4 3.5
透析流速（mL/min） 200 200 200 220
不同剂量 1 3 3 1
游离铂Cmax（μg/mL） 0.42（40） 0.27（40） 0.50（60） 0.53（42.5）
0.22（40） 0.60（70）
0.39（50） 0.86（85）
游离铂AUC0~48 h（μg/h/mL） Not evaluated 15.6（40） 17.6（60） 19.5（42.5）
12.5（40） 23.6（70）
21.5（50） 32.6（85）
表4 伊立替康在透析患者中的药动学参数
Dose（mg/m2） 透析患者（n=15） 正常患者（n=10） P值
50 60 70 50 60 70 ?
AUC（μg.h/mL） SN-38 0.22±0.07 0.19±0.03 0.17±0.03 0.26±0.11 0.18±0.02 0.22±0.08 NS
SN-38G 3.64±1.21 3.42±0.98 2.73±0.88 0.74±0.53 0.64±0.29 0.62±0.25 <0.01
CPT-11 3.55±1.00 3.74±1.28 2.94±1.11 3.47±1.21 3.28±1.33 3.86±2.00 NS
表5 不同肝功能状态时卡培他滨及其代谢产物的药动学参数
? 肝功能正常患者（n=14） 肝功能不全患者（n=13）
肝功能情况 ? ?
肝功能评分 0~2.0 5.0~9.0
总胆红素（μmol/L） 12.0±5.9 112.0±153.0
AST（IU/L） 39.5±41.9 107.0±34.1
ALT（IU/L） 27.1±15.4 112.0±94.0
AP（IU/L） 231.0±150.0 1 816.0±1 096.0
AUC0-∞ ? ?
Capecitabine 7.25 10.70
5′-DFCR 14.10 9.16
5′-DFUR 11.70 14.00
5-FU 0.53 0.61
FBAL 51.10 63.20
Cmax ? ?
Capecitabine 3.95 5.91
5′-DFCR 5.02 3.53
5′-DFUR 4.64 6.19
5-FU 0.22 0.28
FBAL 6.22 6.74
表6 不同肝功能状态时伊立替康及其代谢产物的药动学参数
? 组I 组II 组III 组IV
胆红素（*ULN） ≤1.0 1.10~1.50 1.51~3.00 ≥3.10
剂量（mg/m2） 350 350 175 200 240 100
患者数 7 3 8 3 5 3
伊立替康 ? ? ? ? ? ?
Cmax（μg/mL） 7.12 6.68 4.59 3.85 4.41 3.14
AUC（μg/h/mL） 25.60 34.20 23.00 24.70 30.10 16.40
Cl（L/h/m2） 12.10 9.80 7.20 7.80 7.20 5.50
Vss（L/m2） 78 83 71 91 71 57
t1/2（h） 6.9 9.0 9.3 10.7 8.9 9.3
尿排泄率（%） 15.7 14.4 12.3 10.2 15.2 13.4
SN-38 ? ? ? ? ? ?
Cmax（μg/mL） 0.041 0.068 0.054 0.063 0.060 0.036
AUC（μg/h/mL） 0.435 0.825 0.609 0.709 0.624 0.358
t1/2（h） 14.0 9.7 15.4 21.7 15.8 16.3
尿排泄率（%） 0.14 0.25 0.16 0.12 0.34 0.25
SN-38G ? ? ? ? ? ?
AUC（μg/h/mL） 2.60 3.29 2.95 2.68 2.70 2.12
t1/2（h） 10.3 16.1 18.5 21.4 17.4 17.1
APC ? ? ? ? ? ?
AUC（μg/h/mL） 8.1 17.0 7.4 6.8 7.1 9.8
t1/2（h） 7.2 10.9 11.4 18.6 10.3 14.5
代谢物比例 ? ? ? ? ? ?
AUC SN-38伊立替康 0.018 0.024 0.027 0.030 0.021 0.023
AUC SN-38-G/SN-38 7.5 3.7 6.9 4.7 6.8 5.6
AUC APC/伊立替康 0.32 0.52 0.34 0.28 0.23 0.65
表7 不同肝功能状态时奥沙利铂的药动学参数
参数 组I 组II 组III 组IV 组V（肝移植组）
胆红素 ≤ULN ≤ULN 1.0~3.0 mg/dL >3.0 mg/dL 任意
AST ≤ULN 1~2.5 ULN >2.5 ULN 任意 任意
AP ≤ULN 1~5 ULN >5 ULN 任意 任意
剂量（mg/m2） 130 130 130 130 60
患者数 11 9 6 3 1
Cmax,（μg.Pt/ml） 1.52 1.32 1.13 1.00 1.17
AUC0-∞（μg.h/ml） 12.4 12.4 11.3 35.2 17.1
Vss（L） 567 406 793 574 217
CL（L/h） 20.7 19.8 22.7 17.2 4.6
初始t1/2（h） 0.22 0.28 0.26 0.26 0.2
终末t1/2（h） 22.8 18.5 24.9 31.7 36.1
[1]
Launay-Vacher V, Oudard S, Janus N, et al. Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study [J]. Cancer, 2007, 110(6):1376-1384.
[2]
Launay-Vacher V. Epidemiology of chronic kidney disease in cancer patients: lessons from the IRMA study group [J]. Semin Nephrol, 2010, 30(6):548-556.
[3]
Lichtman SM, Wildiers H, Launay-Vacher V, et al. International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency [J]. Eur J Cancer, 2007, 43(1):14-34.
[4]
Janus N, Thariat J, Boulanger H, et al. Proposal for dosage adjustment and timing of chemotherapy in hemodialyzed patients [J]. Ann Oncol, 2010, 21(7):1395-1403.
[5]
Rengelshausen J, Hull WE, Schwenger V, et al. Pharmacokinetics of 5-fluorouracil and its catabolites determined by 19F nuclear magnetic resonance spectroscopy for a patient on chronic hemodialysis [J]. Am J Kidney Dis, 2002, 39(2):E10.
[6]
Poole C, Gardiner J, Twelves C, et al. Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients [J]. Cancer Chemother Pharmacol, 2002, 49(3):225-234.
[7]
Jhaveri KD, Flombaum C, Shah M, et al. A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR <30 mL/min) and end stage renal disease on hemodialysis [J]. J Oncol Pharm Pract, 2012, 18(1):140-147.
[8]
Labaye J, Sarret D, Duvic C, et al. Renal toxicity of oxaliplatin [J]. Nephrol Dial Transplant, 2005, 20(6):1275.
[9]
Takimoto CH, Remick SC, Sharma S, et al. Administration of oxaliplatin to patients with renal dysfunction: a preliminary report of the national cancer institute organ dysfunction working group [J]. Semin Oncol, 2003, 30(4 Suppl. 15):20-25.
[10]
http: //www.drugfuture.com/fda-ndc/label.aspx?ProductNDC=70860-201#s49
[11]
Katsumata K, Sumi T, Wada T, et al. Oxaliplatin for metastatic colon cancer in a patient with renal failure [J]. Clin Med Oncol, 2008, 2(2):97-101.
[12]
Watayo Y, Kuramochi H, Hayashi K, et al. Drug monitoring during FOLFOX6 therapy in a rectal cancer patient on chronic hemodialysis [J]. Jpn J Clin Oncol, 2010, 40(4):360-364.
[13]
Horimatsu T, Miyamoto S, Morita S, et al. Pharmacokinetics of oxaliplatin in a hemodialytic patient treated with modified FOLFOX-6 plus bevacizumab therapy [J]. Cancer Chemother Pharmacol, 2011, 68(1):263-266.
[14]
Gori S, Lunardi G, Inno A, et al. Pharmacokinetics of oxaliplatin in a hemodialyzed patient: chemotherapy dose adjustment and timing of dialysis [J]. Clin Colorectal Cancer, 2014, 13(4):260-263.
[15]
Janus N, Thariat J, Boulanger H, et al. Proposal for dosage adjustment and timing of chemotherapy in hemodialyzed patients [J]. Ann Oncol, 2010, 21(7):1395-1403.
[16]
Ashizawa T, Iwahori T, Yokoyama T, et al. Irinotecan hydrochloride (CPT-11) in dialysis patients with gastrointestinal cancer [J]. Acta Med Okayama, 2010, 64(1):19.
[17]
Czock D, Rasche FM, Boesler B, et al. Irinotecan in cancer patients with end-stage renal failure [J]. Ann Pharmacother, 2009, 43(2):363-369.
[18]
http: //www.drugfuture.com/fda-ndc/label.aspx?ProductNDC=50242-060
[19]
http: //www.drugfuture.com/fda-ndc/label.aspx?ProductNDC=0024-5840
[20]
http: //www.drugfuture.com/fda-ndc/label.aspx?ProductNDC=0002-7669
[21]
Cao Y, Liao C, Tan A, et al. Meta-analysis of incidence and risk of hypomagnesemia with cetuximab for advanced cancer [J]. Chemotherapy, 2010, 56(6):459-465.
[22]
Chen P, Wang L, Li H, et al. Incidence and risk of hypomagnesemia in advanced cancer patients treated with cetuximab: A meta-analysis [J]. Oncol Lett, 2013, 5(6):1915-1920.
[23]
Nikolic-Tomasevic Z, Jelic S, Cassidy J, et al. Fluoropyrimidine therapy: hyperbilirubinemia as a consequence of hemolysis [J]. Cancer Chemother Pharmacol, 2005, 56(6):594-602.
[24]
Floyd J, Mirza I, Sachs B, et al. Hepatotoxicity of chemotherapy [J]. Semin Oncol, 2006, 33(1):50-67.
[25]
Twelves C, Glynne-Jones R, Cassidy J, et al. Effect of hepatic dysfunction due to liver metastases on the pharmacokinetics of capecitabine and its metabolites [J]. Clin Cancer Res, 1999, 5(7):1696-1702.
[26]
EB/OL] (Accessed on May 04, 2017)

URL    
[27]
Raymond E, Boige V, Faivre S, et al. Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction [J]. J Clin Oncol, 2002, 20(21):4303-4312.
[28]
Venook AP, Enders Klein C, Fleming G, et al. A phase I and pharmacokinetic study of irinotecan in patients with hepatic or renal dysfunction or with prior pelvic radiation: CALGB 9863 [J]. Ann Oncol, 2003, 14(12):1783-1790.
[29]
EB/OL] (Accessed on May 04, 2017)

URL    
[30]
Meyerhardt JA, Kwok A, Ratain MJ, et al. Relationship of baseline serum bilirubin to efficacy and toxicity of single-agent irinotecan in patients with metastatic colorectal cancer [J]. J Clin Oncol, 2004, 22(8):1439-1446.
[31]
Kramar A, Gourgou-Bourgade S, Ychou M. Relationship of serum bilirubin to toxicity in patients with metastatic colorectal cancer treated with single-agent high-dose irinotecan [J]. J Clin Oncol, 2004, 22(8):1439-1446.
[32]
Slade JH, Alattar ML, Fogelman DR, et al. Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury [J]. Clin Colorectal Cancer, 2009, 8(4):225-230.
[33]
Synold TW, Takimoto CH, Doroshow JH, et al. Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study [J]. Clin Cancer Res, 2007, 13(12):3660-3666.
[34]
Grenader T, Goldberg A, Gabizon A. Combination therapy with oxaliplatin and 5-fluorouracil in a patient with severe hepatic dysfunction associated with metastatic adenocarcinoma of the large bowel [J]. Anticancer Drugs, 2009, 20(9):845-847.
[35]
Fakih MG. 5-fluorouracil leucovorin and oxaliplatin (FOLFOX) in the treatment of metastatic colon cancer with severe liver dysfunction [J]. Oncology, 2004, 67(3-4):222-224.
[36]
EB/OL] (Accessed on May 04, 2017)

URL    
[37]
EB/OL] (Accessed on May 04, 2017)

URL    
[38]
US Food and Drug Administration (FDA)-approved prescribing information for ramucirumab available online at EB/OL] (Accessed on May 04, 2017)

URL    
[39]
Madbouly KM, Hussein AM, Zeid A. Colorectal cancer surgery in portal hypertensive patients: does adjuvant oxaliplatin affect prognosis? [J]. Dis Colon Rectum, 2013, 56(5):577-585.
[40]
Gervaz P, Pak-art R, Nivatvongs S, et al. Colorectal adenocarcinoma in cirrhotic patients [J]. J Am Coll Surg, 2003, 196(6):874-879.
[41]
Slade JH, Alattar ML, Fogelman DR, et al. Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury [J]. Clin Colorectal Cancer, 2009, 8(4):225-230.
[42]
Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy [J]. Ann Intern Med, 2009, 150(9):657-658.
[43]
Li HR, Huang JJ, Guo HQ, et al. Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy [J]. J Viral Hepat, 2011, 18(12):877-883.
[44]
Di Bisceglie AM, Lok AS, Martin P, et al. Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg? [J]. Hepatology, 2015, 61(2):703-711.
[45]
Ling WH, Soe PP, Pang AS, et al. Hepatitis B virus reactivation risk varies with different chemotherapy regimens commonly used in solid tumours [J]. Br J Cancer, 2013, 108(10):1931-1935.
[46]
Vento S, Cainelli F, Mirandola F, et al. Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus [J]. Lancet, 1996, 347(8994):92-93.
[47]
Lestuzzi C, Vaccher E, Talamini R, et al. Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk [J]. Ann Oncol, 2014, 25(5):1059-1064.
[48]
Kosmas C, Kallistratos MS, Kopterides P, et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study [J]. J Cancer Res Clin Oncol, 2008, 134(1):75-82.
[49]
Saif MW, Choma A, Salamone SJ, et al. Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes [J]. J Natl Cancer Inst, 2009, 101(22):1543-1552.
[50]
Saif MW, Tomita M, Ledbetter L, et al. Capecitabine-related cardiotoxicity: recognition and management [J]. J Support Oncol, 2008, 6(1):41-48.
[51]
Jensen SA, Sørensen JB. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine [J]. Cancer Chemother Pharmacol, 2006, 58(4):487-493.
[52]
EB/OL] (Accessed on May 04, 2017)

URL    
[53]
Popov I, Carrato A, Sobrero A, et al. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1) [J]. Eur J Cancer, 2008, 44(15):2204-2211.
[54]
Yothers G, O′Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses [J]. J Clin Oncol, 2011, 29(28):3768-3774.
[55]
EB/OL] (Accessed on May 04, 2017)

URL    
[56]
FDA-approved manufacturer′s package insert for bevacizumab available online at EB/OL] (Accessed on May 04, 2017)

URL    
[57]
Hurwitz HI, Saltz LB, Van Cutsem E, et al. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies [J]. J Clin Oncol, 2011, 29(13):1757-1764.
[58]
Choueiri TK, Mayer EL, Je Y, et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab [J]. J Clin Oncol, 2011, 29(6):632-638.
[59]
FDA-approved manufacturer′s labeling information available online at EB/OL] (Accessed on May 04, 2017)

URL    
[60]
Sastre J, Aranda E, MassutíB, et al. Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study [J]. Crit Rev Oncol Hematol, 2009, 70(2):134-144.
[61]
Feliu J, Salud A, Escudero P, et al. XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer [J]. Br J Cancer, 2006, 94(7):969-975.
[62]
Folprecht G, Rougier P, Saltz L, et al. Irinotecan in first line therapy of elderly and non-elderly patients with metastatic colorectal cancer: Meta-analysis of four trials investigating 5-FU and irinotecan(abstract #3578) [J]. Asco Meeting Abstracts, 2006, 24(18suppl):165s.
[63]
Tsai HT, Marshall JL, Weiss SR, et al. Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study [J]. Ann Oncol, 2013, 24(6):1574-1579.
[64]
Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab [J]. J Natl Cancer Inst, 2007, 99(16):1232-1239.
[65]
Seymour MT, Thompson LC, Wasan HS, et al. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial [J]. Lancet, 2011, 377(9779):1749-1759.
[66]
Crosara Teixeira M, Marques DF, Ferrari AC, et al. The effects of palliative chemotherapy in metastatic colorectal cancer patients with an ECOG performance status of 3 and 4 [J]. Clin Colorectal Cancer, 2015, 14(1):52-57.
[1] 康夏, 田浩, 钱进, 高源, 缪洪明, 齐晓伟. 骨织素抑制破骨细胞分化改善肿瘤骨转移中骨溶解的机制研究[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 329-339.
[2] 代莉, 邓恢伟, 郭华静, 黄芙蓉. 术中持续输注艾司氯胺酮对腹腔镜结直肠癌手术患者术后睡眠质量的影响[J]. 中华普通外科学文献(电子版), 2023, 17(06): 408-412.
[3] 王得晨, 杨康, 杨自杰, 归明彬, 屈莲平, 张小凤, 高峰. 结直肠癌微卫星稳定状态和程序性死亡、吲哚胺2,3-双加氧酶关系的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(06): 462-465.
[4] 付佳, 肖海敏, 武曦, 冯涛, 师帅. 年龄校正查尔森合并症指数对腹腔镜结直肠癌围手术期并发症的预测价值[J]. 中华普通外科学文献(电子版), 2023, 17(05): 336-341.
[5] 唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[6] 张生军, 赵阿静, 李守博, 郝祥宏, 刘敏丽. 高糖通过HGF/c-met通路促进结直肠癌侵袭和迁移的实验研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 21-24.
[7] 李婷, 张琳. 血清脂肪酸代谢物及维生素D水平与结直肠癌发生的关系研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 661-665.
[8] 周川鹏, 杨浩, 魏微阳, 王奇, 黄亚强. 微创与标准通道经皮肾镜治疗肾结石合并肾功能不全的对比研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 470-475.
[9] 关旭, 王锡山. 基于外科与免疫视角思考结直肠癌区域淋巴结处理的功与过[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 448-452.
[10] 顾睿祈, 方洪生, 蔡国响. 循环肿瘤DNA检测在结直肠癌诊治中的应用与进展[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 453-459.
[11] 倪文凯, 齐翀, 许小丹, 周燮程, 殷庆章, 蔡元坤. 结直肠癌患者术后发生延迟性肠麻痹的影响因素分析[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 484-489.
[12] 范小彧, 孙司正, 鄂一民, 喻春钊. 梗阻性左半结肠癌不同手术治疗方案的选择应用[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 500-504.
[13] 孙昕, 程海波, 沈卫星. 基于全转录组学探讨仙连解毒方治疗Ⅲ期结直肠癌患者的疗效机制[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 277-283.
[14] 李永胜, 孙家和, 郭书伟, 卢义康, 刘洪洲. 高龄结直肠癌患者根治术后短期并发症及其影响因素[J]. 中华临床医师杂志(电子版), 2023, 17(9): 962-967.
[15] 卓徐鹏, 刘颖, 任菁菁. 感染性疾病与老年人低蛋白血症的相关性研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 896-899.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号