Complications related to arterial infusion chemotherapy in patients with hepatic metastasis from colorectal cancer

Complications of hepatic arterial infusion chemotherapy were analyzed in 30 cases with hepatic metastasis from colorectal cancer from July 1993 to February 2000 in our department. Thirty patients were treated with three kinds of arterial infusion course that mainly consisted of 5-FU. Complications resulting in interruption of therapy occurred in 10 patients (33%), and there was no difference in the incidence rate of complications among the three chemotherapy regimens. The complications with our therapy were hepatic arterial occlusion in two patients, catheter tip dislocation in four patients, fistulus between the hepatic artery and common bile duct in two patients, and fistulus between the hepatic artery and duodenal bulb in two patients. Four patients who had severe complications with fistulus all underwent hepatectomy, especially right hepatic lobectomy in two cases. Sixty percent of our patients had complications after hepatectomy, so regular GIF and DSA are necessary to prevent severe complications after hepatectomy.     

Complications related to hepatic arteria infusion chemotherapy for liver metastasis

Complications from hepatic arterial infusion chemotherapy were analyzed in 27 cases with liver metastasis from colorectal cancer from December 1994 to April 2002 in our department. The method used to place the catheter was laparotomy (LP) in 11 patients, intervention radiology (IVR) in 16 patients. Complications resulting in interruption of therapy occurred in 7 (26%) patients, and the IVR method was associated with a lower rate of complications than the LP method. The complications with the LP method were 3 (11%) cases of hepatic arterial occlusion, and 2 (7.4%) cases of catheter tip dislocation. The best indwelling route for the catheter thus seems to be the IVR method. The IVR method is our first choice for all patients now.     

Evaluation of intermittent hepatic arterial infusion chemotherapy for multiple liver metastasis of colorectal cancer

Five patients with synchronous multiple hepatic metastasis of colorectal cancer were treated with hepatic arterial infusion chemotherapy. All cases received intermittent 5-FU infusion (5-FU 250-1,000 mg/2-3 hrs/1-2 weeks) on an outpatient basis. In the evaluation of 5 cases, 3 PR and 1 NC were observed. One case administered arterial infusion for adjuvant chemotherapy has no recurrence in liver. In two patients, extra-hepatic metastases were found. In conclusion, this therapy was effective and useful for hepatic metastasis. Moreover, other forms of treatment for extra-hepatic metastasis must be used.     

Effect of hepatic arterial infusion chemotherapy for liver metastasis from gastric cancer

We performed hepatic arterial infusion (HAI) chemotherapy for 4 patients with advanced gastric cancer who had undergone curative resection except for liver metastasis. The main antineoplastic drugs were 5-fluorouracil (5-FU), mitomycin C (MMC) and cisplatin (CDDP). A catheter was inserted into the hepatic artery by interventional radiological techniques in 3 patients and operatively in 1 patient. The response rate for 4 patients was 75% (CR2, PR1, PD1). The adverse events were Grade 3/4 nausea and/or vomiting in 2 cases. The HAI chemotherapy was effective and useful for patients with advanced gastric cancer who had no unresectable lesions except for liver metastasis.     

Alternating hepatic arterial infusion and systemic chemotherapy for stage IV colorectal cancer with synchronous liver metastasis

Among 41 patients with synchronous liver metastases of colorectal cancer, 15 patients underwent synchronous resection of their liver metastases and achieved a median survival time (MST) of 1,441 days (versus 748 days for the 26 patients without resection, p=0.038), a median relapse-free survival time of 652 days (MST not reached), and a recurrence rate in the residual liver of 20% (3/15 patients). The alternating hepatic arterial infusion and systemic chemotherapy showed partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive disease (PD) in 1 case (n=15/26). They had an objective response rate of 40% (6/15), tumor control rate (>/= SD) of 93.3% (14/15), one-year progression-free survival rate of 35.7%, 50% time to progression of 270 days, one-year survival rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3 leucopenia was observed in 2/15 patients (13.3%). These results suggest that the present alternating therapy may become a standard regimen for patients in whom synchronous resection of liver metastases is impossible and patients who have stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or at extrahepatic sites such as the lungs.     

Rules to carry out hepatic arterial infusion chemotherapy at home for patients with liver metastasis of colorectal cancer

We analyzed the effectiveness and adverse effects of hepatic arterial infusion chemotherapy (HAI) for patients with liver metastasis of colorectal cancer in order to clarify the rules of HAI. We provided HAI to 72 patients after hepatic resection and to 119 patients with unresectable liver metastases. The preventive effect on hepatic recurrence was recognized in the group administered more than 15 g of 5-FU (total dose). The response rate of patients with unresectable metastases was 60.3%. Adverse effects were observed in 65.8% of the patients. It is important to establish a follow-up system in each hospital to treat the patients as soon as possible when patients develop an adverse reaction.     

Hepatic arterial infusion chemotherapy for liver metastases from colorectal cancer

After randomized studies of hepatic arterial infusion chemotherapy (HAIC) versus systemic chemotherapy for liver metastases from colorectal cancer in the 1980s, the role of HAIC has been unclear and there is still no evidence to support it as the treatment of choice. The high local control, the differences in techniques between Japan and Western countries, the difficulty of detecting pre-treatment extra-hepatic metastases and the fact that HAIC does not control extra-hepatic lesions are the most important points in considering clinical trials of HAIC. Clinical studies on the combination of HAIC using 5-FU and systemic chemotherapy using CPT-11, and then randomized trial of systemic chemotherapy with/without HAIC is required in Japan to reveal the role of HAIC in the management of liver metastases from colorectal cancer. We should understand the importance of our role in this field.     

Validity of two-hour continuous hepatic arterial infusion chemotherapy with low-dose 5-FU for unresectable liver metastasis from colorectal cancer

The significance of hepatic arterial infusion chemotherapy for unresectable liver metastases from colorectal cancer was evaluated in 50 patients, who received either of the following regimens: 1 shot 5-FU + epirubicin + MMC (FAM group); hepatic arterial infusion of 5-FU for 2 hours + MMC (MF group); hepatic arterial infusion of 5-FU for 2 hours (5-FU group). There were no differences in the clinicopathological backgrounds of the patients among the groups. The mean survival time was 10.3 months, 16.0 months and 16.2 months in the FAM, MF and 5-FU groups. The effective percentages were 0%, 40% and 31% in the FAM, MF and 5-FU groups and the survival time of the effective cases was 18.1 months and 21.8 months in the MF and 5-FU groups. The MF group and 5-FU group showed significant improvement in prognosis. Concerning side effects, myelo-suppression and gastrointestinal toxicity appeared frequently in the MF group. In conclusion, 2-hour continuous hepatic arterial infusion with low-dose 5-FU for unresectable liver metastases from colorectal cancer may be helpful for improvement of prognosis.     

Hepatic arterial infusion of IL-2 and chemotherapy for unresectable liver metastasis from colorectal cancer

We administered interleukin (IL)-2 with mitomycin C (MMC) and 5-fluorouracil (5-FU) by hepatic arterial infusion for the treatment of liver recurrence from colorectal cancer. The regimen consisted of continuous hepatic arterial infusion of IL-2 (7 x 10(5) JRU/day)/5-FU (250 mg/day) for 4 weeks. After those 4 weeks, a weekly hepatic arterial infusion of IL-2 (2.1 x 10(6) JRU)/5-FU (250 mg) was performed more than 4 weeks. MMC (4 mg) was given as a bolus weekly. This therapy resulted in partial response (PR) in one case, progressive disease (PD) in one case, and no change (NC) in one case. The toxicity of the therapy was a slight in all cases. We herein report 3 patients treated with hepatic arterial infusion of IL-2 with MMC and 5-FU for liver recurrence from colorectal cancer. This therapy may be a new strategy for metastatic colorectal cancer.     

A case of hepatic arterial infusion chemotherapy with docetaxel for liver metastasis from breast cancer

We experienced a case of hepatic arterial infusion chemotherapy using docetaxel for liver metastasis, which showed no response to CEF therapy, from breast cancer. A 63-year-old woman had undergone modified radical mastectomy for right breast cancer (T2aN1bM0: Stage II) in October, 1995. Six-cycle CMF therapy and toremifene citrate (40 mg/day) were administered as adjuvant therapy, but multiple recurrent tumors in liver, lung, and local site were detected in February 1997. Six-cycle CEF therapy was given for recurrent disease and there was a complete response for lung and local recurrence, but no change in liver metastasis. Chemoendocrine therapies using 5'-DFUR or CMitF in addition to TAM and fadrozole hydrochloride hydrate had developed progressive disease for liver metastasis. A catheter and port kit were operatively inserted and implanted in March 1998. Hepatic arterial infusion of docetaxel (30-40 mg/body/month, one hour administration) was repeated 4 times, once in our clinic. Leukopenia, general fatigue and fever, which were mild and did not require any treatment, appeared as side effects. This treatment reduced multiple liver metastatic sites on abdominal CT finding and was thought to be a partial response. However, the patient had multiple brain metastasis and died on August 2, 1998. While docetaxel, even by systemic administration, has a 36-77% response rate for liver metastasis, arterial infusion might have a good response and mild side effect with a lower dose than by intravenous administration.     

Weekly hepatic arterial infusion of high dose 5-fluorouracil for liver metastasis from colorectal cancer

A weekly infusion of high dose 5-fluorouracil by way of the hepatic artery has been performed in 23 cases with synchronous metastasis from colorectal cancer since 1993. The prognosis in these cases was compared with 94 cases treated without infusion chemotherapy in 94 cases before 1992. The overall one-year and three-year survival rate was 64.8% and 30.2%, respectively, in cases with infusion chemotherapy. The one-year and three-year survival rate was 42.8% and 18.6%, respectively, in cases without infusion chemotherapy. Overall survival rate was significantly different between cases with and without infusion chemotherapy (p < 0.05). In conclusion, weekly infusion chemotherapy resulted in a better survival rate than without infusion chemotherapy.     

Usefulness of hepatic arterial infusion chemotherapy for liver metastasis in gastric cancer]

We have performed intra-hepatic arterial chemotherapy for 9 patients with liver metastasis arising from gastric cancer. We mainly used 5-FU and CDDP as antineoplastic drugs. RESULTS: The median survival after gastrectomy was 600 days. Of 9 cases, 2 showed CR, 4 PR, 2 NC, 1 PD. The response rate was 67%. The 9 cases were classified into 2 groups. One group, the short-term survival group, concised of 5 patients that had no more than 2 years survival and the other, the long-term survival group, consisted 4 patients that had more than 2 years survival. We compared these 2 groups and found no difference in the primary lesions between the 2 groups. The patients in the long-term survival group had fewer and smaller metastatic lesions in the liver than the patients of the short-term survival group. The patients in the long-term survival group had no unresectable lesions except liver metastasis when gastrectomy was performed. However, 2 patients in the short term survival group had unresectable lymphatic involvement at the time gastrectomy was performed. Of 9 patients, 6 died from the extrahepatic lesion. CONCLUSION: The intra-arterial chemotherapy was effective and useful for liver metastasis arising from gastric cancer. However, the majority of patients died from extrahepatic lesions. We should therefore consider the use of systemic chemotherapy with intra-arterial chemotherapy.     

Adjuvant hepatic arterial infusion after resection of hepatic metastasis from colorectal cancer

We examined retrospectively the efficacy of hepatic arterial infusion (HAI) chemotherapy comparing systemic treatment as adjuvant therapy after the curative resection of hepatic metastasis from colorectal cancer. Seventeen cases of HAI and 8 of the systemic treatment were enrolled in this study. We compared the pattern of recurrent sites and the overall survival rate between the two groups. There was no difference in a patients' background. Intrahepatic recurrence rate was lower and extrahepatic recurrence rate was higher in the HAI group, but not significant. The 1-, 3-, and 5-year overall survival rate was 94, 72, and 49% in the HAI group and 100, 100, and 50% in the systemic treatment group (p = 0.29), respectively. HAI chemotherapy did not contribute to the elongation of survival time in comparison with systemic treatment. This study indicates that there is no efficacy of HAI alone after the resection of hepatic metastasis from colorectal cancer and that there is need to use systemic chemotherapy together with HAI to prevent an extrahepatic recurrence.     

Evaluation of arterial infusion chemotherapy for liver metastasis from gastric cancer

We evaluated the effectiveness of arterial infusion chemotherapy for liver metastasis from gastric cancer. Nineteen patients (9 synchronous cases, 10 metachronous cases) were treated with hepatic arterial infusion chemotherapy (HAIC). The response rate was 26% (CR 3, PR 2, PD 14), and the median survival time was 357 days after the diagnosis of liver metastasis. The treatment was discontinued in 8 patients because of treatment associated complications and disease progression. Absence of extrahepatic lesion, response of HAIC, and hepatectomy did not improve the prognosis. The combination of systemic chemotherapy with HAIC tended to improve the prognosis. It may be necessary to reevaluate HAIC as a treatment modality for liver metastasis from gastric cancer.     

Hepatectomy and intraarterial infusion chemotherapy for liver metastasis from colorectal cancer

Hepatectomy and intraarterial chemotherapy for liver metastasis from colorectal cancer have been performed in our department. Intraarterial infusion chemotherapy has also been performed for unresectable liver metastasis. One hundred twenty-seven cases of liver metastasis from colorectal cancer were studied. The cases were divided into groups according to radicability of the original colorectal cancer, whether or not hepatectomy was performed, and whether or not they received intraarterial chemotherapy. Group I is cur C of origin. Group II is cur A or B without hepatectomy. Group III is cur A or B with hepatectomy. Each group was divided into a group without intraarterial chemotherapy (A) and a group with it (B). IA 23 cases, IB 13 cases, IIA 14 cases, IIB 21 cases, IIIA 28 cases, and IIIB 28 cases. The survival rate of group III was better than that of group II. The survival rate of group II was better than that of group I. There was no significant difference in survival rates between IA and IB. The survival rate of group IIB was significantly better than that of group IIA. The survival rate of group IIIB was significantly better than that of group III A. Hepatectomy and intraarterial chemotherapy after hepatectomy for liver metastasis from colorectal cancer were effective.     

Evaluation of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer

We evaluated the effect of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer. Of 405 patients undergoing colectomy in our department from July 1993 to February 2002, 38 had liver metastasis. We performed catheterization intra-operatively or postoperatively, and intra-arterial infusion chemotherapy was given for liver metastasis from colorectal cancer. Thirty-eight patients were treated with four different arterial infusion courses that mainly consisted of 5-FU. The 5-year survival rate was 8%. Maximal survival period was 68 months, and mean survival was 22 months. The effective rate was 20% Intra-arterial infusion chemotherapy was a useful treatment for liver metastasis from colorectal cancer. Resection of the liver metastasis was the first choice for operative liver metastases from colorectal cancer, and we performed intra-arterial infusion chemotherapy for patients postoperatively or patients with non-operative liver metastasis.     

Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis

Objective:To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis (CRCLM)patients treated by transarterial chemoembolization (TACE) and sustained hepatic arterial infusion chemotherapy (HAIC).Methods:Between 2006 and 2015,162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study,including 110 males and 52 females,with a median age of 60 (range,26-83) years.Prognostic factors were assessed with Log-rank test,Cox univariate and multivariate analyses.Results:The median survival time (MST) and median progression-free survival (PFS) of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively.Normal serum carbohydrate antigen 19-9 (CA19-9,＜37 U/mL) (P＜0.001) and carbohydrate antigen 72-4 (CA72-4,＜6.7 U/mL) (P=0.026),combination with other local treatment (liver radiotherapy or liver radiofrequency ablation) (P=0.034) and response to TACE/HAIC (P＜0.001) were significant factors related to survival after TACE/HAIC in univariate analysis.A multivariate analysis revealed that normal serum CA19-9 (P＜0.001),response to TACF/HAIC (P＜0.001) and combination with other local treatment (P=0.001) were independent factors among them.Conclusions:Our findings indicate that serum CA19-9 ＜37 U/mL and response to TACE/HAIC are significant prognostic indicators for this combined treatment,and treated with other local treatment could reach a considerable survival benefit for CRCLM.This could be useful for making decisions regarding the treatment of CRCLM.     

Hepatic arterial infusion of chemotherapy for hepatic metastases from colorectal cancer.

BACKGROUND: Sixty percent of colon cancer patients develop liver metastasis. Only 25% of those have potentially resectable hepatic metastases, and approximately 58% of those patients relapse. METHODS: We review the indications and the technical aspects of hepatic artery infusion (HAI) of chemotherapy, as well as the efficacy, morbidity, and outcomes. RESULTS: HAI of chemotherapy has been used following hepatic metastasectomy, in patients with unresectable metastases, or in combination with other agents. Floxuridine, the chemotherapeutic agent most studied, is administered through an implantable subcutaneous infusion pump connected to a surgically placed hepatic artery catheter, which delivers the chemotherapeutic agents at a slow fixed rate. Treatment-related toxicities include chemical hepatitis, biliary sclerosis, and peptic ulceration. Some trials report a survival benefit for HAI over systemic chemotherapy with acceptable toxicity. CONCLUSIONS: Regional perfusion chemotherapy can be logistically and technically complicated to deliver. The development of newer systemic agents with superior efficacy in the treatment of metastatic colorectal cancer will likely diminish the role of regional perfusion therapy in the future.     

Indication for hepatic resection after hepatic arterial infusion chemotherapy for multiple liver metastases of colorectal cancer

The indications for hepatic resection after hepatic arterial infusion chemotherapy (HAI) for unresectable metastatic liver tumor of colorectal cancer were analyzed from the surgical outcome of hepatic resections in 23 cases of hepatic resection after HAI. The mean duration of HAI until hepatic resection was 7.4 months (5-14 months). The total dose of 5-FU was 25.7 +/- 8.0 g for a CR + PR group and 14.0 +/- 3.5 g for a NC + PD group. There was a significant difference between two groups (p < 0.01). The group in which serum CEA level normalized after HAI (the normal CEA group) included 7 patients, and the group in which serum CEA level did not normalize (the high CEA level group) had 9 patients. The total dose of 5-FU was 30.0 +/- 7.6 g in the normal CEA level group and 19.1 +/- 6.9 g in the high CEA level group. There was a significant difference between the two groups. The 3-year survival rate was 40.0% in the group with the duration of HAI for longer than 8 months (n = 10) and 0% in the group with the duration of HAI for shorter than 8 months (n = 7). The 3-year survival rate was 66.7% in the normal CEA level group (n = 3) and 0% in the high CEA level group (n = 8). The surgical outcome was better in the HAI for longer than 8 month and normal CEA groups.     

An update on hepatic arterial infusion chemotherapy for colorectal cancer

Hepatic metastases are a frequent complication of colorectal cancer (CRC), affecting over half of all CRC patients. Resection of isolated metastases can result in long-term survival, but the majority of patients relapse, and most have unresectable disease. Hepatic arterial infusion (HAI) chemotherapy delivers high concentrations of cytotoxic agents directly to liver metastases with minimal systemic toxicities. Advances in surgical techniques, development of fully implantable pumps, and modification of drug regimens have decreased complications and improved patient tolerability. Randomized trials comparing HAI with systemic chemotherapy have demonstrated superior response rates and times to hepatic progression for unresectable disease, and have shown better times to progression and overall survival rates in the adjuvant setting following hepatic resection. HAI chemotherapy has unique toxicities, including chemical hepatitis and biliary sclerosis, which can be mitigated by the addition of dexamethasone to therapy. In an attempt to prevent extrahepatic progression, combinations of HAI with systemic chemotherapy, including newer agents such as irinotecan and oxaliplatin, are currently being investigated, with promising early results.