氟脲苷肝动脉持续灌注联合草酸铂静脉化疗治疗肝转移癌

目的观察经肝动脉灌注氟脲苷(FUDR)同时联合草酸铂(OXA)静脉化疗治疗肝转移癌的疗效及毒副反应.方法 28例结直肠癌或胃癌肝转移患者,经肝动脉灌注FUDR,静脉输入OXA治疗2～6个周期.所有病例均行术前术后CT扫描评价治疗效果.随访44个月,评价疗效、生存期及毒副反应.结果总有效率为42.8%,中位生存时间(MST)为25个月,出现肝转移后的MST为15.5个月,1,2,3年生存率分别为89.3%、67.8%和25.0%.结论采用新的化疗方案FUDR加OXA局部联合全身同时化疗安全有效,患者生存期得以延长.     

立体定向放疗联合或不联合经导管动脉化疗栓塞治疗不可切除结直肠癌肝转移的回顾性研究

目的:比较单纯立体定向放疗或经导管动脉栓塞化疗联合立体定向放疗治疗不可手术结直肠癌肝转移的疗效及安全性。 方法:回顾性分析23例不可手术结直肠癌肝转移患者资料,所有患者曾接受一线标准的全身化疗,化疗后肝脏病灶接受或者经导管动脉栓塞化疗。单纯接受立体定向治疗的13例患者为SBRT组,接受经导管动脉栓塞化疗和立体定向放疗的10例患者为TACE-SBRT组,比较两组患者的肝内病灶局部治疗后的疾病缓解率(RR)、疾病控制率(DCR)和疾病进展时间（TTP）,同时观察并发症发生情况,采用Kaplan-Meier、Log-rank检验,Cox回归模型分析中位无进展生存时间(mPFS)和总生存时间(mOS)。结果:SBRT组和TACE-SBRT组的局部治疗反应RR和DCR无统计学意义（P=0.685）;与SBRT组相比,TACE-SBRT组的无疾病进展时间延长,差异有统计学意义（11.77±1.56 vs 25.40±5.81,P=0.019）。TACE-SBRT的mPFS优于SBRT组,分别为17.4个月和15.1个月（P<0.05）,但是mOS两组之间无统计学意义。同时,仅有1例患者出现Ⅲ级肝功能损伤,治疗后恢复。Cox 回归比例风险模型分析确诊肝转移时CEA水平和同时性转移是无进展生存期和总生存期的预后不良因素(P<0.05)。结论:全身化疗后联合SBRT和TACE治疗不可切除的结直肠癌肝转移是一种安全有效的方法,是一种可接受的替代治疗方法,但仍需进一步研究。     

雷替曲塞联合奥沙利铂行肝动脉化疗栓塞后灌注术治疗老年结直肠癌肝转移

目的：观察雷替曲塞联合奥沙利铂行肝动脉化疗栓塞后灌注术治疗老年结直肠癌肝转移的疗效及毒副反应。方法选取我院收治的56例结直肠癌肝转移老年患者,随机分为对照组、观察组2组,每组28例。对照组单纯采用雷替曲塞联合奥沙利铂肝动脉化疗栓塞治疗,观察组则采用雷替曲塞联合奥沙利铂肝动脉化疗栓塞后灌注术治疗,比较2组疗效及毒副反应。结果观察组治疗总有效率为7143%,明显高于对照组的4286%（P ＜005）;观察组1 a 生存率为9643%,明显高于对照组的7500%（P ＜005）。观察组疾病进展时间为为（84±03）个月,明显高于对照组的（61±04）个月（P ＜005）。观察组总生存时间为（156±06）月,略高于对照组的（148±09）个月,但差异无统计学意义（P ＞ O 05）。骨髓抑制、转氨酶升高、恶心呕吐、周围神经毒性为2组的主要毒副反应。结论在结直肠癌肝转移患者临床治疗中,采用雷替曲塞联合奥沙利铂行肝动脉化疗栓塞后灌注术可提高疗效,改善患者生存。     

经门静脉和肝动脉灌注化疗治疗不可切除的结直肠癌肝转移的临床研究

[目的]探讨不可切除的结直肠癌肝转移患者的治疗方法.[方法] 97例不可切除的结直肠癌肝转移患者分为治疗组47例和对照组50例.对照组结直肠癌切除术后2周开始FOLFOX方案全身化疗.治疗组在结直肠癌切除术中及术后经门静脉和肝动脉化疗泵行5-Fu肝脏局部灌注化疗,全身化疗和其余治疗同对照组.[结果]两组治疗后病灶数目和大小均减小,CEA、CA199均降低,两组差异显著(P＜0.05).治疗组中位生存时间33.7个月,1、3、5年生存率分别为81.2％、42.8％和10.6％,对照组中位生存时间21.8个月,1、3、5年生存率分别为64.0％、19.7％和0,两组差异显著(P＜0.05);两组术后并发症及不良反应发生率无明显差异(P＞0.05).[结论]经门静脉和肝动脉灌注化疗对于不可切除的结直肠癌肝转移瘤是安全有效的,可以延长患者的生存期,改善患者预后.     

肝动脉灌注在结直肠癌肝转移治疗中的应用现状及前景

肝转移是结直肠癌主要的转移模式及治疗关键。相对于全身化疗,肝动脉灌注（hepatic arterial infusion, HAI）给药方式可使肝脏局部药物浓度升高,而外周血液中药物浓度较低,全身不良反应相对较低。《中国肿瘤临床》于2015年第20期邀请中山大学肿瘤防治中心李宇红教授综述了肝动脉灌注化疗在结直肠癌肝转移的转化化疗、肝切除术后辅助治疗及结直肠癌根治性切除术后的肝转移预防方面的作用与价值。     

肝动脉灌注在结直肠癌肝转移治疗中的应用现状及前景

结直肠癌（colorectal cancer ，CRC ）是中国最常见的恶性肿瘤之一，肝转移是其主要的转移模式及治疗关键。相对于全身化疗，肝动脉灌注（hepatic arterial infusion，HAI）给药方式可使肝脏局部药物浓度升高，而外周血液中药物浓度较低，全身不良反应相对较低。HAI 化疗在肠癌肝转移的转化化疗、肝切除术后辅助化疗以及肠癌根治性切除术后的肝转移预防方面显示出一定的应用前景。本文就HAI 在肠癌肝转移的治疗现状及前景做一综述。      

肝动脉插管及腹腔注药联合化疗治疗结直肠癌肝转移28例报告

探讨肝动脉插管及腹腔注药联合化疗治疗结直肠癌肝转移的治疗效果。方法　 2 8例结直肠癌 ,分别行左半结肠、右半结肠或经腹直肠癌根治性切除术后 ,行肝动脉插管及腹腔置管 ,药盒埋植于皮下 ,经药盒给药化疗。结果　本组 2 8例 ,完全缓解(CR) 2例 ,部分缓解 (PR) 13例 ,总有效率 (CR PR) 5 3 6 %。生存期最短 2个月 ,最长者 3年以上至今存活。结论　肝动脉插管及腹腔注药联合化疗治疗结直肠癌肝转移 ,毒副作用小 ,疗效确切 ,是治疗结直肠癌肝转移有效的治疗方法。     

肝动脉插管及腹腔注药联合化疗治疗结直肠癌肝转移28例报告

目的 探讨肝动脉插管及腹腔注药联合化疗治疗结直肠癌肝转移的治疗效果。方法 ２８例结直肠癌，分别行左半结肠、右半结肠或经腹直肠癌要治性切除术后，行肝动脉插管及腹腔置管，药合里植于皮下，经药盒给药化疗。结果 本组２８例，完全缓解（ＣＲ）２例，部分缓解（ＰＲ）１３例，总有效率（ＣＲ＋ＰＲ）５３．６％。生存期最短２个月，最长者３年以上至今存活。结论 肝动脉插管及腹腔注药联合化疗治疗结直肠癌肝转移，毒副作用     

初始可切除结直肠癌肝转移术后辅助化疗的研究进展

结直肠癌是目前全球第三大常见的恶性肿瘤，大约有50%的患者在病程中发生肝转移。结直肠癌肝转移(CRLM)分为初始可切除和不可切除。肝切除术目前被认为是治疗CRLM唯一潜在的治愈方法，患者5年生存率约为37%～40%。但肝切除术后这部分患者仍然存在较高的复发风险，因此选择合适的辅助治疗尤为重要。目前CRLM患者术后辅助化疗存在争议，以往前瞻性临床研究发现术后辅助化疗能延长无进展生存时间，但无法改善总生存时间。最近部分研究在化疗基础上联合靶向药物或肝动脉灌注化疗(HAIC)等应用于术后CRLM患者，以期获得更好的疗效。本文就可切除CRLM术后辅助化疗的应用现状及研究进展作一综述。     

微波组织凝固联合全身化疗治疗结直肠癌肝转移17例分析

肝脏是结直肠癌最主要的转移部位,发生率高达15%～20%.Adam等[1]报道,结直肠癌患者50%发生肝转移.肝转移是结直肠癌治疗失败、影响预后和长期生存的主要原因.我院应用B超定位经皮肝穿刺微波组织凝固（percutaneous microwave coagulation therapy, PMCT,PMCT）加全身化疗（FOLFOX方案）治疗结直肠癌肝转移17例,结果报道如下.     

Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. RESULTS: The MTD for patients in group A was Oxal 100 mg/m(2), CPT-11 150 mg/m(2), and FUDR 0.12 mg/kg x 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m(2), LV 400 mg/m(2), and FU 1,400 mg/m(2) by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. CONCLUSION: Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.     

Debulking treatment with CT-guided percutaneous radiofrequency ablation and hepatic artery infusion of floxuridine improves survival of patients with unresectable pulmonary and hepatic metastases of colorectal cancer

The survival of most patients with both unresectable hepatic and pulmonary metastases of colorectal cancer is poor. In this retrospective study, we investigated the efficacy of computed tomography （CT）-guided radiofrequency ablation （RFA） and systemic chemotherapy plus hepatic artery infusion of floxuridine （HAI-FUDR）. Sixty-one patients were selected from 1,136 patients with pulmonary and hepatic metastases from colorectal cancer. Patients were treated with RFA and systemic chemotherapy plus HAI-FUDR （ablation group, n=39） or systemic chemotherapy plus HAI-FUDR （FUDR group, n=22）. Patients in the two groups were matched by sex, age, number of metastases, and calendar year of RFA or FUDR. Survival data were evaluated by using univariate and multivariate analyses. Clinical characteristics were comparable between the two groups. Al patients in the ablation group underwent RFA and chemotherapy. Median fol ow-up was 56.8 months. The 1-, 3-, and 5-year overall survival （OS） rates were 97%, 64%, and 37%, respectively, for the ablation group, and 82%, 32%, and 19%, respectively, for the FUDR group. The 1-, 3-, and 5-year survival rates after metastasis were 97%, 49%, and 26%for the ablation group, and 72%, 24%, and 24%for the FUDR group, respectively. The median OS times were 45 and 25 months for the ablation and FUDR groups, respectively. In the multivariate analysis, treatment al ocation was a favorable independent prognostic factor for OS （P = 0.001） and survival after metastasis （P = 0.009）. These data suggest that the addition of RFA to systemic chemotherapy plus HAI-FUDR improves the survival of patients with both unresectable hepatic and pulmonary metastases from colorectal cancer.     

Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer.

PURPOSE: Patients who undergo resection of liver metastases from colorectal cancer have an average 2-year survival of 65%. With hepatic arterial infusion (HAI) plus systemic fluorouracil and leucovorin, 2-year survival increased to 86%. For further improvement in both local and systemic control, combinations of new systemic drugs with HAI are being explored. The purpose of this study was to determine the maximum-tolerated dose (MTD) of systemic irinotecan (CPT-11) and HAI floxuridine (FUDR) plus dexamethasone (DEX) as combination adjuvant therapy after liver resection. PATIENTS AND METHODS: Ninety-six patients who underwent complete resection of liver metastases from colorectal cancer were treated with six monthly cycles of HAI FUDR plus DEX for 14 days of each 4-week cycle plus escalating doses of systemic CPT-11. The primary end points of the phase I/II study were the MTD and efficacy of this regimen. RESULTS: The MTD for combined systemic CPT-11 and HAI FUDR was CPT-11 at 200 mg/m2 every other week and FUDR at 0.12 mg/kg x pump volume / pump flow rate. The dose-limiting toxicities were diarrhea and neutropenia. With a median follow-up time of 26 months, the 2-year survival rate is 89%. All of the 27 patients who were treated at the MTD are alive. CONCLUSION: In patients who undergo resection of liver metastases from colorectal cancer, adding systemic CPT-11 to HAI therapy in an adjuvant regimen is feasible. This regimen seems to have comparable activity to fluorouracil and leucovorin, but further studies are needed to assess whether it improves local control or decreases extrahepatic recurrences.     

Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of concurrent systemic irinotecan and hepatic arterial infusion (HAI) of floxuridine (FUDR) and dexamethasone in patients with unresectable hepatic metastases from colorectal cancer, to determine the safety of this combination in patients who have undergone cryosurgery, and to evaluate the pharmacokinetic effects of HAI FUDR on the metabolism of irinotecan. PATIENTS AND METHODS: Forty-six previously treated patients with unresectable liver metastases and no known extrahepatic disease were treated concurrently with intravenous irinotecan weekly for 3 weeks and with HAI of FUDR and dexamethasone for 14 days (both were recycled in 28 days). Parallel cohorts of patients treated with or without cryosurgery were entered at escalating dose levels. RESULTS: The MTD for patients who did not undergo cryosurgery was 100 mg/m2 of irinotecan weekly for 3 weeks every 4 weeks with concurrent HAI FUDR (0.16 mg/kg/d x pump volume/flow rate) plus dexamethasone for 14 days of a 28-day cycle. The dose-limiting toxicities were diarrhea and neutropenia. The response rate (complete and partial) among all patients who did not undergo cryosurgery was 74%. All patients in the cryosurgery group responded, and seven of the eight cryosurgery patients developed normal positron emission tomography scans after chemotherapy. HAI FUDR had no effect on the metabolism of irinotecan. CONCLUSION: Combination therapy with HAI FUDR and dexamethasone plus systemic irinotecan may be safely administered to patients with unresectable hepatic metastases from colorectal cancer. The MTD has been reached for patients with unresectable disease, and we continue to investigate the MTD for patients who have undergone cryosurgery. Although the main objective of this study was to evaluate the toxicity of the combined regimen, a high response rate (74%) was observed.     

Hepatic arterial infusion and systemic chemotherapy after multiple metastasectomy in patients with colorectal carcinoma metastatic to the liver: a North Central Cancer Treatment Group (NCCTG) phase II study, 92-46-52

BackgroundPatients with multiple liver metastases from colorectal cancer are at high risk of recurrence after resection. Hepatic artery infusion (HAI) alternating with systemic therapy after surgical resection may improve survival after surgery.MethodsPatients with liver-only metastases from colorectal cancer amenable to resection/cryoablation were eligible. Previous adjuvant chemotherapy for a completely resected primary tumor was allowed. Alternating courses of HAI and systemic therapy included floxuridine (FUDR) by HAI. Systemic chemotherapy consisted of bolus leucovorin (LV) plus 5-fluorouracil (5-FU).ResultsForty-nine patients had complete resection of their liver metastases, with 44% having more than 4 hepatic metastases and 78% having bilobar disease. Thirty-six patients had HAI FUDR alternating with systemic therapy. Patients received a median of 3.5 cycles (range, 1-4) and 3 cycles (range, 0-6) of therapy with HAI FUDR and systemic therapy, respectively. At the time of final analysis the estimated median disease-free survival and hepatic disease-free survival was 1.2 years (95% confidence interval [CI], 0.9-2.1) and 1.8 years (95% CI, 1.8-not available), respectively. Eleven patients (31%) were alive at this writing. All surviving patients had a minimum of 5.5 years of follow-up.ConclusionThis trial of adjuvant chemotherapy in patients who underwent complete resection with unfavorable characteristics demonstrates apparent improvement in outcome compared with historical series treated with surgery alone. However the results of this trial and other randomized trials of HAI do not appear to support its use at this time because of the development of more effective systemic options.     

Hepatic arterial infusion plus systemic irinotecan in patients with unresectable hepatic metastases from colorectal cancer previously treated with systemic oxaliplatin: a retrospective analysis.

BACKGROUND: Response rates to systemic chemotherapy are low after tumor progression on oxaliplatin regimens. Hepatic arterial infusion (HAI) therapy in patients with tumor progression is a viable alternative. PATIENTS AND METHODS: Thirty-nine heavily pre-treated patients (all receiving prior oxaliplatin) with unresectable colorectal hepatic metastases were treated with systemic CPT-11 and concurrent HAI floxuridine (FUDR) and dexamethasone (DEX). RESULTS: Partial responses were seen in 44% of patients. Median time to hepatic progression was 8.6 months, and median time to overall progression was 6.5 months. Median survival from time of initiation of HAI was 20.1 months [95% confidence interval (CI) 16.9-21.4] and from the initiation of treatment of metastatic disease, 32.01 months (95% CI 29.1-34.6). After a median follow-up of 19.1 months, seven patients (18%) proceeded to potentially curative surgery. Grade 3/4 toxic effects included neutropenia (13%), diarrhea (15%), intra-abdominal hemorrhage (2%), and bleeding duodenal ulcer (2%). Elevated liver function tests were seen, including bilirubin concentration >3 mg/dl (7%), alkaline phosphatase 2X baseline (20%), and aspartate aminotransferase >3X baseline (26%). CONCLUSIONS: HAI FUDR/DEX plus systemic CPT-11 achieves a response rate of 44% and a median overall survival of 20 months in heavily pre-treated patients with colorectal hepatic metastases all receiving previous oxaliplatin; 18% of patients proceeded to surgical resection or ablation.     

A phase II study of radiofrequency ablation of unresectable metastatic colorectal cancer with hepatic arterial infusion pump chemotherapy

BACKGROUND: Adjuvant hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve disease-free survival for colorectal cancer liver metastases. It is unclear if this improvement can be extrapolated to unresectable liver metastases that undergo RFA. The aim of this study was to evaluate the combination of RFA and HAI chemotherapy for unresectable liver metastases. METHODS: Phase II study was conducted from November 2000 to July 2003 evaluating the use of complete extirpation by RFA, or resection/ablation with adjuvant HAI consisting of FUDR for 6 months. RESULTS: Twenty-one patients had successful resection and/or RFA with HAI pump, which included treatment for 100 liver metastases (22 resected, 78 ablated; mean 4.8 tumors/patient). Four of 21 patients completed the full 6-month course of HAI. Six of these patients had 12 adverse events related to HAIP, most commonly elevated liver enzymes. After a median follow-up of 24 months, the median liver specific disease-free and overall survival rates for the entire group were 17 and 30 months, respectively. CONCLUSIONS: Given the complications and toxicity associated with HAI pump chemotherapy, adjuvant HAI chemotherapy after RFA of liver metastases may not be warranted as a first line treatment option.     

Hepatic arterial infusion of floxuridine and dexamethasone plus high-dose Mitomycin C for patients with unresectable hepatic metastases from colorectal carcinoma

BACKGROUND: In vitro data suggest increased cytotoxicity with Mitomycin C (Mit-C) and Floxuridine (FUDR). Based on these data, we performed a phase II trial of hepatic arterial infusion (HAI) of FUDR and Dexamethasone (Dex) plus high-dose Mit-C for patients with unresectable hepatic metastases from colorectal carcinoma. METHODS: High-dose Mit-C (15 mg/m2) was added via the pump sideport to HAI FUDR and Dex for 14 days of a 28-day cycle. Mit-C was given on days 1 and 29, and FUDR was given indefinitely until disease progression or discontinuation of therapy due to toxicity. RESULTS: Sixty-three patients with unresectable liver metastases were entered. The chemotherapy-na?ve group (n = 26) and those previously treated (n = 37) had similar response and median survival: 73% and 70%, and 23 and 20 months, respectively. The major toxicities were liver bilomas (7.9%), elevation in bilirubin level >3 (22%), and biliary sclerosis (9.5%). Hematologic and gastrointestinal toxicity was less than 2%. CONCLUSION: The addition of high-dose Mit-C to HAI FUDR and Dex produced a high response rate even in previously treated patients. The median survival was 21 months even though half the patients were previously treated with chemotherapy. Biliary toxicity was higher than expected; therefore, alternatives to high dose Mit-C should be investigated when exploring additions to HAI therapy with FUDR and Dex.     

First-line treatment with hepatic arterial infusion plus capecitabine vs capecitabine alone for elderly patients with unresectable colorectal liver metastases

This study aimed to compare the efficacy and safety of HAI fluoropyrimidine (FUDR)/capecitabine or single capecitabine as first-line treatment for elderly patients with unresectable colorectal liver metastases (CLMs). Fifty-one elderly patients with liver-only CLMs were eligible for enrollment. Patients were divided into HAI FUDR /capecitabine group and single capecitabine group randomly. The primary endpoint was median survival time (MST), defined as the time from the date of catheter implantation to the date of death or the date of the last follow-up. The secondary endpoint was objective antitumor response and adverse events. The HAI pump was implanted before chemotherapy. All patients received a 3-week cycle of oral capecitabin. In Group A, the RR and DCR were both 95.8%. In Group B, the RR and DCR were 48.1% and 81.5%, respectively. There was significant difference between the RRs of the 2 groups (P < 0.001). But there was no significant difference between the DCRs of the 2 groups (P = 0.053). There was a statistical difference between the MSTs of the 2 groups (18.5 vs.13 months, P = 0.0312). HAI FUDR combined with oral capecitabine as the first-line treatment for elderly patients with CLMs has promising efficacy and safety.     

What is the potential role of hepatic arterial infusion chemo-therapy in the current armamentorium against colorectal cancer

The management of colorectal cancer patients with liver metastases is a common clinical problem. If patients can undergo resection of liver metastases, long-term survival can be achieved. Converting a patient from unresectable to resectable, however, remains a major challenge. The majority of patients who undergo liver resection for colorectal metastases recur; therefore, adjuvant treatment following resection should be considered. Emerging literature suggests that hepatic arterial infusion (HAI) can be combined with systemic chemotherapy. Both therapies can be given at nearly full doses, thus improving resectability and outcomes for patients with colorectal liver metastases. HAI plus systemic can also be a useful option for adjuvant treatment after hepatic resection.Key Words: Liver metastases, colorectal cancer, hepatic arterial infusion, conversion treatment, adjuvant