切换至 "中华医学电子期刊资源库"
高级检索
中华介入放射学电子杂志

中华介入放射学电子杂志 ›› 2017, Vol. 05 ›› Issue (04) : 273 -281. doi: 10.3877/cma.j.issn.2095-5782.2017.04.015

所属专题： 专题评论； 文献；

循证医学

伊立替康载药微球治疗结肠癌肝转移瘤的系统评价
徐新建1, 滕飞2, 杜洪涛3,†()   
  1. 1. 317000　浙江省台州医院血管介入中心
    2. 315000　浙江省宁波市第一人民医院放射科
    3. 221000　江苏省徐州中心医院放射科
  • 收稿日期:2017-01-06 出版日期:2017-11-01
  • 通信作者: 杜洪涛

A systematic review of transarterial chemoembolization with irinotecan beads in treatment of colorectal liver metastases

Xinjian Xu1, Fei Teng2, Hongtao Du3,†()   

  1. 1. Department of Interventional Radiology, Taizhou Hospital of Zhejiang Province, Taizhou 317000, China
    2. Department of Interventional Radiology, The No, 1 People's Hospital of Ningbo, Zhejiang Province, Ningbo 315000, China
    3. Radiology, XuZhou Central Hospital, Jiangshu Province, Xuzhou 221000 China
  • Received:2017-01-06 Published:2017-11-01
  • Corresponding author: Hongtao Du
  • About author:
    Corresponding author: Du Hongtao, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

徐新建, 滕飞, 杜洪涛. 伊立替康载药微球治疗结肠癌肝转移瘤的系统评价[J]. 中华介入放射学电子杂志, 2017, 05(04): 273-281.

Xinjian Xu, Fei Teng, Hongtao Du. A systematic review of transarterial chemoembolization with irinotecan beads in treatment of colorectal liver metastases[J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2017, 05(04): 273-281.

目的：

系统评价伊立替康载药微球栓塞（DEBIRI）治疗结肠癌肝转移（CRLM）患者的疗效及安全性。

方法：

搜索DEBIRI治疗CRLM的相关文献，收集其研究指标包括治疗不良反应、药物代谢动力学、肿瘤治疗反应以及总体生存率等，并进行系统评价综述。

结果：

共纳入8项观察性研究及2项随机对照试验（RCT）研究，其中观察性研究共纳入578例患者。栓塞后综合征是最常见的治疗不良反应。栓塞治疗后1~2 h血浆内伊立替康水平最高。肿瘤治疗有效率报道差异较大，中位生存期为5.4~25个月不等。2项RCT研究表明DEBIRI治疗CRLM在肿瘤总反应率及无进展生存期方面优于5-氟尿嘧啶/四氢叶酸/伊立替康化疗方案（FOLFOX）。

结论：

对无手术根治机会的CRLM患者，尤其是对一线治疗无效的患者，DEBIRI是全身化疗或局部治疗无效后的新型替代疗法。

关键词: 结肠癌肝转移, 伊立替康, 载药微球
Objective:

To systematicly evaluate the efficacy and safety of transarterial embolization with drug-eluting beads of irinotecan (DEBIRI) for treatment of unresectable colorectal liver metastasis (CRLM) .

Methods:

A comprehensive search of medical literature identified the studies describing the use of DEBIRI in treatment of CRLM. Data describing adverse events, pharmacokinetics, tumor response, and overall survival were collected.

Results:

Eight observational studies and two randomized controlled trials (RCTs) were reviewed. A total of 578 patients were included in the descriptive analysis of observational studies. Postembolization syndrome was the most common adverse event. Peak plasma levels of irinotecan were observed after 1~2 h of administration. Wide variations in tumor response were observed. The median survival time ranged from 5.4 months to 25 months. In the two RCTs, treatment with DEBIRI was superior to systemic chemotherapy with 5-fluorouracil/leucovorin/irinotecan in terms of overall response rate and progression-free survival.

Conclusions:

For patients with unresectable CRLM, particularly after failure to respond to first-line regimens, DEBIRI represents a novel alternative to systemic chemotherapy alone or other local treatments.

Key words: Colorectal liver metastasis, Irinotecan, Drug-eluting beads
表1 纳入文献资料
作者，发表年份 例数 年龄（岁） 纳入标准 排除标准 早期化疗史 中位生存期 治疗6个月反应率 不良反应事件
Martin 2011 55 60 (34～82) 确诊肝脏转移瘤；患者曾有化疗病史 NS FOLFOX联合贝伐单抗(n= 17);FOLFOX联合贝伐单抗、FOLFIRI、西妥昔单抗(n =14); ≥3种化疗方案(n=14) 19个月 CR(n=7); PR(n=21); SD(n=19); PD(n=8); DOD(n=5) 总事件数(n=28)；Grade1/2(n=21); Grade≥3(n=7);肝功能异常(n=3)；胆囊炎(n=1)；厌食症(n=1)；心肌梗死致死(n=1)
Aliberti 2011 82 61.8 (46～82) 组织学检查证实肝脏转移瘤；手术史；肝脏肿瘤负荷(25%-50%) ECOG评分<2；营养损害；肝肾储备功能欠佳；腹水；门静脉血栓 ≥2种全身化疗联合PD方案；化疗不敏感 25月(6~34月)；2例患者术后14月及18月接受根治切除治疗 NS Grade1/2(NS); Grade3疼痛(n=20)
Vogl 2012 77 61 (36～78) 不可切除肝转移瘤；手术禁忌或患者拒绝手术；毒副作用；化疗不敏感 肝外转移；肝脏肿瘤负荷>70%；肝肾储备功能欠佳；门静脉部分/完全血栓形成；呼吸/心脏衰竭 所有患者（奥沙利铂） 22.5月(7~70月)；部分合并残余肿瘤患者接受激光热疗 NS 总事件数(NS)；均为Grade1/2.
Eichler 2012 11 64 (45～85) 1-8个肝内转移瘤；ECOG评分≤1；预期生存期>6月；肝肾储备功能良好 肝外转移；肿瘤/肝脏体积比>30；伊立替康禁忌；活动性细菌、病毒、真菌感染；伴发其他恶性肿瘤 8例患者 NS PD(n=7); SD(n=2); PR(n=2) 总事件数(n=41)；疼痛(63%)；恶心(22%);呕吐(19.5%)；61%轻度，31%中度。
Martin 2012 10 63 (48～84) 肝内转移瘤数量≥1，直径>1cm；肝脏肿瘤负荷≥80%；肿瘤/肝脏体积比<60%；门脉主干通畅；ECOG评分≤2；预期生存期>3月 根治治疗（切除或射频消融） 无 15.2月(6.5~45.5月)；4例患者接受根治性手术切除 CR(n=8); DOD(n=1); Not assessed(n=1) 总事件数(n=99)；高血压(80%)；腹痛(40%);恶心(40%)；Grade1/2(n= 9); Grade3(n=1)
Fiorentini 2012(RCT) 36 64 (44～77) 组织学检查证实不可切除的肝脏转移瘤；肝脏肿瘤负荷(<0%) 肝外转移；先前肝肿瘤消融病史；栓塞治疗病史；腹水；肝肾储备功能欠佳 ≥2种全身化疗方案 NS NS 总事件数(n=77)；Grade2/3；疼痛(30%);呕吐(25%)；疲乏(20%)；发热(15%)
作者，发表年份 例数 年龄（岁） 纳入标准 排除标准 早期化疗史 中位生存期 治疗6个月反应率 不良反应事件
M. Stutz 2015 27 57 (45～82) 组织学检查证实不可切除的肝脏转移瘤；化疗不敏感；ECOG评分≤2 NS 15例患者曾接受手术治疗（肝叶切除，射频消融或联合治疗）；所有患者对至少1种化疗方案不敏感（1≤n≤5） 5.4月(1.1~22.7月） NS 总事件数(n=51)；疼痛(16/27，59.3%)；恶心(8/27，30%);呕吐(6/26，22%)；疲乏(9/27，33%)。
Roberto Iezzi 2015 20 65.8 (52～77) 年龄≥18岁；不可切除肝转移瘤；肝脏肿瘤负荷≥80%；肿瘤/肝脏体积比< 60%;化疗不敏感；ECOG评分≤2；肝肾储备功能良好；预期生存期>3月 曾接受卡培他滨化疗方案；伊立替康禁忌；严重外周血管及心脏疾病；严重合并症如恶性高血压，充血性心衰，慢性肾病等；脑转移瘤；妊娠或哺乳期妇女 4例患者接受肝叶/段切除术；所有患者对至少2种化疗方案不敏感 7.3月 PR(n=2); SD(n=10); 总事件数(n=66)；Grade1/2(n=64):恶心/呕吐(n=8)；疲乏(n=8)；疼痛(n=4) Grade3/4(n=2):腹泻(n=1)；心绞痛(n=1)
Robert C 2015(RCT) 40 57 年龄≥18岁；组织学证实肝转移瘤；肝脏肿瘤负荷≥80%；肿瘤/肝脏体积比<60%;所有患者均为初次化疗；ECOG评分≤2 适合根治治疗（如手术或射频消融治疗） 无 NS CR/PR(n=33); SD(n=3); PD(n=5) 总事件数(n=973)；血液/淋巴系统事件(n=90):心脏事件(n=10)；胃肠道事件(n=206)；肝胆事件(n=13)：感染事件(n=27)；肺事件(n=46)；皮肤事件(n=37);血管事件(n=38)；神经系统事件(75)
? ? ? ? ? ? ? ? grade3/4(n=144)
Neal Bhutiani 2016 296 63 (32～86) 年龄≥18岁；不可切除肝转移瘤；肝脏肿瘤负荷>50%；化疗不敏感；明确描述化疗方案；ECOG评分≤2 对比剂过敏；难以纠正的凝血功能障碍；严重的外周血管疾病；肝外肿瘤负荷>50%；肿瘤/肝脏体积比>75%;重度肝功能异常；活动性感染 所有患者对至少1种化疗方案不敏感 NS CR(n=74); PR(n=69); SD(n=76); PD(n=106); DOD(n=29) 总事件数(n=105)；Grade1/2(n=74)疼痛(n=20)；恶心(n =15):呕吐(n=17)；肝功能异常/衰竭(n=9);厌食(n=3)：感染(n=6)；心律失常(n=4)；呼吸衰竭(n=1)
? ? ? ? ? ? ? ? Grade3/4(n=31)
表2 纳入文献伊立替康载药微球资料
作者，发表年份 治疗方案 微球类型 微球直径（μm） 伊立替康浓度(mg/ml) 平均总剂量(mg) 每次栓塞治疗平均剂量(mg) 每例患者平均（中位）栓塞次数
Martin 2011 16例(16/55)患者DEBIRI联合卡培他滨或灌注5-FU DC 100-300, 300-500，500-700 25 185 100 1.8(2)
Aliberti 2011 DEBIRI单药治疗 DC 100-300, 300-500 50 352 156 2.3(2.2)
Vogl DEBIRI单药治疗；每四周接受一次 SM NS NS NS 150 mg/m2 BSA 3.2
2012 DEBIRI（≥3次） ? ? ? ? ? ?
Eichler 2012 每三周接受一次DEBIRI（≤4次） DC 100-300,300-500 50 293 73 4(4)
Martin 0/14天标准化疗方案(FOLFOX)，7/ DC 100-300 50 280 100 2.8(2.5)
2012 21天接受DEBIRI ? ? ? ? ? ?
Fiorentini 2012(RCT) DEBIRI单药治疗；1月后剂量加倍 DC 100-300 50 400 200 2(2)
M. Stutz 2015 DEBIRI单药治疗 DC 100-300 50 138 106 1.3
Roberto Iezzi 2015 DEBIRI联合卡培他滨 DC <150 50 270 100 2.7(3)
Robert C 2015(RCT) 0/14天标准化疗方案(FOLFOX)，7/ 21天接受DEBIR DC 100-300 50 290 100 2.9(4)
Neal Bhutiani 2016 DEBIRI单药治疗 DC 75-150,100-300，300-500, 500-700 50 230 100 2.3
表3 纳入文献栓塞技术方面资料
作者，发表年份 首次造影 栓塞靶区选择 栓塞终点
Martin 2011 股动脉穿刺肝动脉造影确定肝动脉起点 肝叶动脉水平栓塞 NS
Aliberti 2011 选择性动脉插管造影评估肝动脉血供及肠系膜动脉造影排除附属肝动脉；导管头端超过胃十二指肠动脉开口水平 肝叶/段动脉水平栓塞 5分钟内缓慢推注微球，栓塞终点NS
Vogl 2012 选择性动脉插管造影评估肝动脉血供；导管头超过胃十二指肠动脉开口水平 段/亚段水平栓塞 血管造影见血流停滞时停止载药微球栓塞
Eichler 2012 诊断性造影评估肝动脉血供及门脉通畅性 超选择性插管，避开胆囊动脉至病灶近端 出现血流停滞时停止载药微球栓塞，未使用其他栓塞物质
Martin 2012 股动脉穿刺肝动脉造影确定肝动脉起点 肝叶动脉水平栓塞 NS
Fiorentini 2012(RCT) NS 超选择性至肿瘤滋养血管栓塞 NS
M. Stutz 2015 股动脉穿刺肝动脉造影确定肝动脉起点 肝叶/段动脉水平栓塞 造影见血流停滞时停止载药微球栓塞
Roberto Iezzi 2015 诊断性造影评估肝动脉血供及门脉通畅性 肝叶动脉水平栓塞 造影见血流停滞时停止载药微球栓塞
Robert C 2015(RCT) 股动脉穿刺肝动脉造影确定肝动脉起点 肝叶动脉水平栓塞 NS
Neal Bhutiani 2016 股动脉穿刺肝动脉造影确定肝动脉起点 肝叶动脉水平栓塞 NS
图1 文献检索及筛选流程图
1
Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. Ca A Cancer Journal for Clinicians, 2005, 55(2):74-108.
2
Slesser AA, Georgiou P, Brown G, et al. The tumour biology of synchronous and metachronous colorectal liver metastases: a systematic review[J]. Clin Exp Metastasis,2013, 30(4):457-470. doi: 10.1007/s10585-012-9551-8.
3
Scheele J, Stang R, Altendorf-Hofmann A, et al. Resection of colorectal metastases[J]. World J Surg, 1995, 19(1):59-71.
4
Gayowski TJ, Iwatsuki S, Madariaga JR, et al. Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors[J]. Surgery, 1994, 116(4):703-710.
5
Ekberg H, Tranberg KG, Andersson R，et al. Determinants of survival in liver resection for colorectal secondaries[J]. Br J Surg, 1986, 73(9):727-731.
6
Manfredi S, Lepage C, Hatem C，et al. Epidemiology and management of liver metastases from colorectal cancer[J]. Ann Surg, 2006, 244(2):254-259. doi: 10.1097/01.sla.0000217629.94941.cf
7
Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer[J]. J Clin Oncol, 2004, 22(22):23-30. doi: 10.1200/JCO.2004.09.046.
8
Fyfe GA, Hurwitz H, Fehrenbacher L, et al. Bevacizumab plus irinotecan/5-FU/leucovorin for treatment of metastatic colorectal cancer results in survival benefit in all pre-specified patient subgroups[J]. J Clin Oncol, 2004, 22(14):3617.
9
Sobrero AF, Maurel J, Fehrenbacher L, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer[J]. J Clin Oncol, 2008, 26(14):2311-2319. doi: 10.1200/JCO.2007.13.1193.
10
Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma[J]. Hepatology，2005，42(5):1208-1236. doi: 10.1002/hep.20933.
11
Yao KA, Talamonti MS, Nemcek A, et al. Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors[J]. Surgery, 2001, 130(4):677-682. doi: 10.1067/msy.2001.117377.
12
Aliberti C, Tilli M, Benea G, et al. Trans-arterial chemoembolization（TACE）of liver metastases from colorectal cancer using irinotecan-eluting beads: preliminary results[J]. Anticancer Res., 2006, 26(26):3793-3795.
13
Eichler K, Zangos S, Mack MG，et al. First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads(DEBIRI)[J]. Int J Oncol，2012，41(4):1213-1220. doi: 10.3892/ijo.2012.1572.
14
Martin RC, Joshi J, Robbins K，et al. Hepatic intra-arterial injection of drug-eluting bead，irinotecan（DEBIRI）in unresectable colorectal liver metastases refractory to systemic chemotherapy: results of multi-institutional study[J]. Ann Surg Oncol, 2011, 18(1):192-198. doi:10.1245/s10434-010-1288-5.
15
Stutz M, Mamo A, Valenti D，et al. Real-life report on chemoembolization using DEBIRI for liver metastases from colorectal cancer[J]. Gastroenterol Res Pract，2015，2015:715102. doi：10.1155/2015/715102.
16
Martin RC 2nd, Scoggins C R, Tomalty D, et al. Irinotecan drug-eluting beads in the treatment of chemo-naive unresectable colorectal liver metastasis with concomitant systemic fluorouracil and oxaliplatin: results of pharmacokinetics and phase I trial[J]. J Gastrointest Surg, 2012, 16(8):1531-1538. doi: 10.1007/s11605-012-1892-8.
17
Vogl TJ, Jost A, Noureldin NA, et al. Repeated transarterial chemoembolisation using different chemotherapeutic drug combinations followed by MR-guided laser-induced thermotherapy in patients with liver metastases of colorectal carcinoma[J]. Br J Cancer, 2012, 106(7):1274-1279 doi:10.1038/bjc.2012.69.
18
Bhutiani N, Akinwande O, Martin RC 2nd. Efficacy and toxicity of hepatic intra-arterial drug-eluting（Irinotecan）bead（DEBIRI）therapy in irinotecan-refractory unresectable colorectal liver metastases[J]. World J Surg, 2016,40(5):1178-1190. doi: 10.1007/s00268-015-3386-9.
19
Iezzi R, Marsico VA, Guerra A, et al. Trans-arterial chemoembolization with irinotecan-loaded drug-eluting beads （DEBIRI）and capecitabine in refractory liver prevalent colorectal metastases: A phase II single-center study[J]. Cardiovasc Intervent Radiol，2015, 38(6):1523-1531. doi:10.1007/s00270-015-1080-9.
20
Fiorentini G, Aliberti C, Tilli M, et al. Intra-arterial infusion of irinotecan-loaded drug-eluting beads（DEBIRI）versus intravenous therapy（FOLFIRI）for hepatic metastases from colorectal cancer: final results of a phase III study[J]. Anticancer Res, 2012, 32(4):1387-1395.
21
Martin RC 2nd, Scoggins CR, Schreeder M, et al. Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis[J]. Cancer, 2015,121(20):3649-3658. doi: 10.1002/cncr.29534.
22
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)[J]. Eur J Cancer，2009，45(2):228-247. doi: 10.1016/j.ejca.2008.10.026.
23
Rees M, Tekkis PP, Welsh FK, et al. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients[J]. Ann Surg, 2008, 247(1):125-135 doi: 10.1097/SLA.0b013e31815aa2c2.
24
Smith MD, Mccall JL. Systematic review of tumour number and outcome after radical treatment of colorectal liver metastases[J]. Br J Surg, 2009, 96(10):1101-1113. doi: 10.1002/bjs.6735.
25
Bhattacharjya S, Aggarwal R, Davidson BR. Intensive follow-up after liver resection for colorectal liver metastases: results of combined serial tumour marker estimations and computed tomography of the chest and abdomen-a prospective study[J]. Br J Cancer, 2006, 95(1):21-26. doi:10.1038/sj.bjc.6603219.
26
Tang Y, Taylor RR, Gonzalez MV, et al. Evaluation of irinotecan drug-eluting beads: a new drug-device combination product for the chemoembolization of hepatic metastases[J]. J Control Release, 2006, 116(2):e55-e56. doi:10.1016/j.jconrel.2006.09.047.
27
Baize N, Gerard B, Bleiberg H, et al. Long-term survival of patients downstaged by oxaliplatin and 5-fluorouracil combination followed by rescue surgery for unresectable colorectal liver metastases[J]. Gastroenterol Clin Biol, 2006, 30(12):1349-1353.
28
Adam R, Delvart V, Pascal G, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy[J]. Ann Surg, 2004, 240:644-657.
29
Lam VW, Spiro C, Laurence JM, et al. A systematic review of clinical response and survival outcomes of downsizing systemic chemotherapy and rescue liver surgery in patients with initially unresectable colorectal liver metastases[J]. Ann Surg Oncol, 2012, 19(4):1292-1301. doi:10.1245/s10434-011-2061-0.
30
Bower M, Metzger T, Robbins K, et al. Surgical downstaging and neo-adjuvant therapy in metastatic colorectal carcinoma with irinotecan drug-eluting beads: a multi-institutional study[J]. HPB, 2010, 12(1):31-36. doi:10.1111/j.1477-2574.2009.00117.x.
[1] 向俊西, 杨魁, 王光辉, 李龙, 张月浪, 吴胤英, 杨威, 佘军军, 刘青光, 姚英民, 郭成. 腹腔镜手术治疗结肠癌肝转移并盆腔转移一例[J]. 中华腔镜外科杂志(电子版), 2021, 14(04): 241-244.
[2] 曹耿飞, 张海潇, 顾俊鹏, 朱帝文, 鲍应军, 阿斯哈尔·哈斯木, 任伟新. 载药微球栓塞联合索拉非尼治疗不可切除肝癌安全性和疗效[J]. 中华肝脏外科手术学电子杂志, 2021, 10(01): 43-47.
[3] 高博, 陈卓妙语, 王秋生. 基于权重基因共表达分析的结肠癌肝转移相关基因挖掘与验证[J]. 中华结直肠疾病电子杂志, 2020, 09(04): 363-369.
[4] 马玉洁, 陈冬娜, 梁向伟, 孙永琨. 雷替曲塞联合伊立替康治疗晚期结直肠癌的临床观察[J]. 中华结直肠疾病电子杂志, 2020, 09(04): 349-354.
[5] 吴振海, 曲秀娟, 曲晶磊, 刘静, 张敬东, 刘云鹏. 伊立替康联合雷替曲塞方案二线治疗晚期结直肠癌的疗效与安全性分析：一项探索性研究[J]. 中华结直肠疾病电子杂志, 2018, 07(05): 463-467.
[6] 马超, 金焰, 段希斌, 曹巍, 邢国臣, 易善永, 李学民, 王晓飞. 药物转运体基因多态性对伊立替康治疗结直肠癌患者所致严重不良反应的影响[J]. 中华结直肠疾病电子杂志, 2018, 07(03): 257-261.
[7] 盛静, 梅勇, 夏佩, 王晓林. 乌苯美司联合伊立替康二线治疗晚期胃癌的临床研究[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 317-321.
[8] 曾嘉, 何东风. 介入栓塞材料在肝癌治疗中的研究进展[J]. 中华介入放射学电子杂志, 2023, 11(01): 62-67.
[9] 李臻, 纪坤, 王彩鸿, 宋丽杰, 李鑫, 詹鹏超, 石洋, 韩新巍. DEB-TACE治疗神经内分泌肿瘤肝转移的疗效初探[J]. 中华介入放射学电子杂志, 2021, 09(01): 25-30.
[10] 韩建军, 宋金龙, 谢印法, 刘景洲, 徐慧荣, 张昊, 孙元栋, 朱海涛. 载药微球治疗恶性肝脏肿瘤的全程管理[J]. 中华介入放射学电子杂志, 2019, 07(01): 7-16.
[11] 刘松, 李强, 于广计, 王庆东. CalliSpheres载药微球治疗老年肺鳞状细胞癌疗效分析[J]. 中华老年病研究电子杂志, 2020, 07(03): 12-16.
[12] 李莹, 刘芬. 伊立替康联合顺铂化疗对进展期胃癌复治患者的疗效评价[J]. 中华卫生应急电子杂志, 2017, 03(06): 343-347.
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