The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.     

Management after hepatectomy of colorectal cancer metastases to the liver--intrahepatic arterial infusion chemotherapy and repeated hepatectomy

Before Dec. 1993, we resected 17 patients with hepatic metastases from colorectal cancer. Hepatic recurrences developed in 82% patients who had been given mitomycin C or doxorubicin by hepatic-artery. The one-, 3- and 5-year survival rate after surgery was, 88%, 18% and 12%, respectively. Therefore, some new types of adjuvant therapy were needed to improve survival after surgery. This is a retrospective study to determine whether preventive intrahepatic artery infusion chemotherapy (HAI) and repeated hepatectomy are of benefit for patients with hepatic metastases from colorectal cancer who underwent hepatectomy. Thirty-five patients with hepatic metastases from colorectal cancer underwent hepatectomy and were administered 1,500 mg of 5-FU 10 times via the hepatic artery for 5 hrs every 1-2 weeks to prevent hepatic recurrence after Jan. 1994. Nine patients underwent repeated hepatectomy, then HAL following the operation. Non-resectable recurrence were treated by HAI. The amounts of the infused 5-FU dose were 8.5-46.5 g (mean 23 g) and 17-31 times HAI (mean 22 times). Survival rates were 81, 67, 67% and 24%, respectively, after 1, 2, 3 and 4 years. Hepatic disease-free interval rates were 49.3% and 32.5%, respectively, after 1 and 2 years. Preventive HAI could not control hepatic recurrence but prognosis after hepatectomy was improved by these modalities compared with treatment before Dec. 1993. Survival rates of 9 patients who underwent repeated hepatectomy were 89, 89% and 37%, respectively, after 1, 3 and 4 years. The prognosis of patients with hepatic metastases from colorectal cancer was improved by HAI and repeated hepatectomy, but further studies should be undertaken to improve preventive HAI.     

Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial.

PURPOSE: A multicentric randomized study that compared patients who received intrahepatic arterial infusion (HAI) to a group of patients who did not receive HAI (control group) was performed for unresectable hepatic metastases from primary colorectal carcinoma. PATIENTS AND METHODS: One hundred sixty-six patients were assigned randomly to HAI of floxuridine (5 fluoro-2'deoxyuridine [FUDR]) 0.3 mg/kg/d for 14 days every 4 weeks or to the control group; this latter group, depending on the investigator's choice, was either under observation or received systemic fluorouracil (5-FU). The same regimen of systemic 5-FU also was administered to the HAI group in the event of extrahepatic progression. No crossover from the control group to the HAI group was permitted. The mean duration of follow-up was 54 months (range, 31 to 72), and 163 patients were analyzed. RESULTS: A significant improvement was observed in the survival rate for the 81 patients assigned to HAI group (P less than .02) with a 1-year survival rate of 64% versus 44% in the control group (82 patients). The 2-year survival rate was 23% versus 13%. The median survival was 15 months versus 11 months for the HAI group and the control group, respectively. Survival was better for patients with a less than 30% liver involvement, and for those treated in more specialized centers. The hepatotoxic effects of HAI were observed in 47 patients (chemical hepatitis [n = 28], and biliary sclerosis [n = 19]). The 1-year rate of sclerosing cholangitis was equal to 25%. Gastrointestinal toxicity was infrequent and consisted of gastritis or diarrhea. CONCLUSIONS: Therapy with HAI of FUDR improves the survival of patients with liver metastases over colorectal carcinoma. However, the methods that are used to diminish the toxicity of HAI and efficient systemic chemotherapy, such as a combination of 5-FU and leucovorin, are required to prevent extrahepatic metastases.     

Evaluation of hepatic resection following hepatic arterial infusion chemotherapy for colorectal liver metastases

We evaluated the significance of hepatectomy following hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. The prognosis of 4 cases with initially resectable tumors was discouraging, indicating no benefit of preoperative HAI for resectable tumors. The 2- and 3-year survival of patients who underwent hepatectomy after downstaging by HAI of originally unresectable metastases were 100% and 67%, respectively, suggesting that hepatectomy combined with HAI is a promising modality for those patients. However, it seems that the control of extrahepatic disease and decision making for the timing for surgical therapy are issues requiring improvement.     

Final results of a randomized clinical trial of adjuvant intraportal chemotherapy for colorectal cancer: Intraportal Chemotherapy for Colorectal Cancer Group

The purpose of the present multi-center collaborative study was to elucidate the efficacy of intraportal chemotherapy with the combination of 5-FU and MMC for the prevention of liver recurrence after resection for colorectal cancer. A total of 125 patients with Stage II, III, and IV colorectal cancer were enrolled in this study between June 1993 and December 1995. Of them, 45 patients were randomized to a portal group: 10 mg/body of mitomycin one shot portal infusion, before and after 500 mg/m2 of 5-FU per 24 h for 7 days portal infusion followed by administration of oral 5-FU. Fifty-three patients were randomized to a control group: oral administration of 5-FU. Twelve patients suffered from temporary mild liver damage. One patient (2%) in the portal group and 6 patients (11%) in the control group developed liver metastases; there was not a significant difference between these two groups regarding development of liver metastases. There was also no significant difference by tumor stage between the portal and control groups regarding development of liver metastases. The 5-year survival rate and 5-year disease-free survival were 84.3% and 81.9%, respectively, in the portal group, and 70.7% and 72.4%, respectively, in the control group; the difference was not significant. Although there was not a significant difference between the portal and control groups regarding the prognosis in stage II, there was a significant difference between the portal and control groups regarding the 5-year disease free survival in stage III (81.1% vs 54.2%). These results suggest that intraportal chemotherapy is effective for stage III colorectal cancer.     

Evaluation of prophylactic hepatic arterial infusion chemotherapy after curative hepatectomy for metastatic colorectal cancer

We evaluated the effect of hepatic arterial infusion (HAI) chemotherapy after curative resection of liver metastases of colorectal cancer. A total of 161 patients underwent curative resection of liver metastases. Among them, 50 patients underwent HAI of 5-FU, and 111 patients had no HAI therapy. The 50% disease-free survival time (50% DFS) was 758 days and 342 days in the HAI group and the non-HAI group (logrank test, p<0.01), and the 50% overall survival time (50% OS) was 978 days versus 730 days (p<0.05), respectively. Among the 71 patients with multiple resectable metastases (H2 or H3), the HAI group had a significantly superior 50% DFS. HAI therapy seems to be an effective form of adjuvant chemotherapy after hepatic resection of metastatic colorectal cancer.     

Results of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5-fluorouracil infusion and oral UFT after resection of hepatic colorectal metastases

BACKGROUND: Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluorouracil (5-FU) infusion and UFT. UFT enhanced plasma 5-FU concentration and antitumor effects during 5-FU infusion. The authors report on their experiences with arterial 5-FU infusion and UFT after resection of hepatic colorectal secondaries. METHODS: Fifty-eight patients were divided into two groups after hepatectomy. Group A, 30 patients, underwent hepatic arterial infusion (HAI) via implantable port system with perfusion 5-FU for 2 consecutive days per week at 600 mg/m(2)/day, and oral administration of UFT at 400 mg/day for 5-7 days per week, repeated 10 times, and Group B, 28 patients, underwent oral administration of UFT at 400 mg/day for 6 months. All the patients were managed at the outpatient clinic at Hyogo College of Medicine, and recurrence, survival, and toxicity were documented. Plasma 5-FU concentrations during chemotherapy were detected using high performance liquid chromatography. RESULTS: Maximum plasma concentrations of 5-FU in Group A reached 144.0 ng/mL and in Group B 58.7 ng/mL. Cumulative 5-year survival rate after hepatectomy in Group A was 59% and in Group B was 27%. (P = 0.00001) HAI-PMC drastically decreased hepatic recurrence (median hepatic recurrence free times were 34.2 months in Group A vs. 18.4 months in Group B; P = 0.00002). Grade 3 toxicity in Group A was found in 3 patients CONCLUSIONS: Pharmacokinetic modulating chemotherapy was designed as a uracil-related biochemical modulation. HAI-PMC significantly decreased hepatic recurrence after curative resection. This new chemotherapy concept significantly improved prognosis in patients with hepatic colorectal metastases.     

Adjuvant hepatic arterial infusion after curative resection of colorectal liver metastases using removable intra-arterial catheters with shape-memory alloy

BACKGROUND AND OBJECTIVES: Although there are some reports that adjuvant hepatic arterial infusion (HAI) chemotherapy reduces the hepatic recurrence following curative resection of colorectal liver metastases, problems of indwelling catheters after chemotherapy cessation remains unsolved. The usefulness of adjuvant HAI was investigated using a removable port-catheter system. METHODS: Spiral catheterstrade mark were attempted to be placed in 17 patients who underwent curative hepatectomy. The catheter contains a special shape-memory alloy at its tip, which allows stable fixation to the vascular wall without coiling so the catheter can be removed if necessary. 5-fluorouracil (5-FU) in total dose of 12 g was intra-arterially administered. RESULTS: W spiral catheterstrade mark were successfully placed in the hepatic artery by percutaneous approach in 82% of the patients. All patients underwent scheduled chemotherapy without serious adverse events. Reservoir-catheter system was removed easily and uneventfully after discontinuation of the chemotherapy. 3D-CT angiography revealed that the hepatic artery was well preserved with short-term chemotherapy. Postoperative hepatic recurrence was observed only in 18% of the patients with the median follow-up time of 19.9 months. CONCLUSIONS: Prophylactic 5-FU HAI using W spiral cathetertrade mark and subsequent catheter extirpation is a promising strategy following curative resection of colorectal liver metastases.     

Present and future of home anti-cancer chemotherapy for unresectable recurrence of colorectal cancer

Continuous hepatic arterial infusion chemotherapy (HAI) was performed for 100 colorectal cancer patients with unresectable liver metastases in our outpatient clinic. The administration schedule was 5-FU 250 mg/day for 7 days every other week. In this study, 93 cases were evaluable. The average dose of 5-FU was 24 g (3.0-66.5 g). The response rate was 59.1% (CR: 4 cases, PR: 51 cases, NC: 12 cases and PD: 26 cases). The prognostic outcome was significantly prolonged in the effective cases (50% survival duration was as follows: CR: 764 days, PR: 620 days, NC: 255 days and PD: 152 days). The complication rate with HAI was 15.1%, but nobody died from these complications. Hepatectomy after HAI was performed in 19 cases (20.4%) because of the effect of HAI. The three-year survival rate was 35.3% for HAI with hepatectomy and 3.8% for only HAI. There was statistically significant difference (p < 0.0001) between these two groups. Hepatectomy after HAI is a new strategy for unresectable liver metastasis of colorectal cancer. Recently, we performed home systemic chemotherapy using 5-FU for 3 recurrent patients of colorectal cancer and were able to continue this therapy safely for more than 2 months.     

Prophylactic hepatic arterial infusion chemotherapy for the prevention of liver metastasis in patients with colon carcinoma: a randomized control trial

BACKGROUND: The liver is the most frequent site of recurrence after curative resection in patients with colon carcinoma. For liver metastasis, a high response rate can be achieved with hepatic arterial infusion (HAI) chemotherapy. In the current study, the authors administered 5-fluorouracil (5-FU) as adjuvant chemotherapy by HAI to patients with colon carcinoma without liver metastases and studied its effects on recurrence in the liver and survival. METHODS: A total of 316 patients with preoperative Stage II or Stage III colon carcinoma (according to the 1997 revision of the International Union Against Cancer TNM staging system) were randomly assigned to receive surgery plus 3-week continuous HAI of 5-FU or surgery alone. There were 305 eligible patients, of whom the 119 patients assigned to the HAI arm actually received 5-FU. The primary endpoint was disease-free survival, whereas the secondary endpoints were overall survival and liver metastasis-free survival. Analysis was by intent to treat. RESULTS: There were no significant differences noted in morbidity between the two treatment arms. During the follow-up period (median, 59.0 months), the incidence of liver metastasis was significantly decreased in the HAI arm whereas there were no significant differences reported between the 2 arms with regard to the frequency of metastasis at other sites. In the HAI arm, the risk ratio for recurrence was 0.40 (95% confidence interval [95% CI], 0.24-0.64; P=0.0002), the risk ratio for death was 0.37 (95% CI, 0.21-0.67; P=0.0009), and the risk ratio for liver metastasis was 0.38 (95% CI, 0.22-0.66; P=0.0005). These differences were found to be significant only for patients with Stage III disease. Toxicities were mild. CONCLUSIONS: A schedule of 3-week HAI of 5-FU given as adjuvant chemotherapy to patients with Stage III colon carcinoma appeared to contribute to a significant decrease in the frequency of liver metastases and was associated with an improved survival rate.     

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.     

Efficacy of adjuvant hepatic arterial infusion chemotherapy following resection of colorectal liver metastases

PURPOSE: The aim of this study is to evaluate the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) following liver resection on the frequency of residual liver recurrence and overall survival. PATIENTS AND METHODS: During 1992 to 1997, 84 patients with liver metastasis from colorectal cancer resected curatively had undergone adjuvant HAIC. The regimen of the HAIC is 1,500 mg of 5-FU by 24-hr continuous infusion once a week for eight weeks. 37 cases in the HAIC group, including patients given more than 7 g of 5-FU, were compared with the control group. RESULT: The cumulative 5-year liver recurrence-free ratios were 72.6% in the HAIC group and 29.8% in the control group (p = 0.0005). The cumulative 5-year survival ratios were 61.4% in the HAIC group and 28.0% in the control group (p = 0.0069). Multivariate analysis revealed that more than 5 mm of surgical margin and adjuvant HAIC significantly decreased the risk of recurrences in residual liver. CONCLUSION: Adjuvant HAIC is an effective procedure to prevent recurrence in residual liver and improve the prognosis of patients with liver metastasis from colorectal cancer.     

Hepatic arterial infusion (HAI) chemotherapy achieved a complete response (CR) for multiple liver metastases of colorectal cancer--two case reports

We encountered two cases of concurrent multiple liver metastases of colorectal cancer in two patients who achieved a complete response (CR) to hepatic arterial infusion (HAI) chemotherapy. The first case is a 64-year old man who was found to have anemia, and a diagnosis of ascending colon cancer was made. There were 6 metastatic lesions in both lobes of the liver. A right hemicolectomy was performed. Postoperative chemotherapy consisted of 2 g of oral UFT-E as well as 3 mg of CDDP and 500 mg of 5-FU administered by HAI. The metastatic lesions disappeared after 9 courses of chemotherapy were carried out. A partial hepatectomy was performed in the scarred area. Histopathological examination revealed no cancer cells. No recurrence has been observed for 4 years and 10 months since achieving CR. The second case is a 69-year-old man who had thin stool and bloody stool. Rectal cancer was diagnosed. Five metastatic lesions were noted in both lobes of the liver. A low anterior resection was performed. l-LV 25 mg and 5-FU 500 mg were given postoperatively by HAI. After three courses of chemotherapy postoperatively, metastatic lesions disappeared. No recurrence has been noted for 2 years and 1 month since achieving CR. HAI chemotherapy is considered one of the useful treatment options for patients with multiple liver metastases of colorectal cancer.     

Efficacy of 5-FU hepatic arterial infusion with l-leucovorin for patients with unresectable colorectal liver metastasis

We investigated the efficacy of 5-FU hepatic artery infusion (HAI)for patients with unresectable colorectal liver metastasis. Fifteen patients who received HAI between June 2004 and December 2006 were studied. HAI was attempted as first-line chemotherapy in seven patients(Group A)and as second-line or more in eight(Group B). The response rate, time to progression, survival and toxicity were compared with those of 39 patients treated with systemic chemotherapy(18 as first-line: Group C, 21 as second-line or more: Group D). Response rate was 85.7%, 35.7%, 50.0%, and 4.8% in Groups A, B, C, and D, respectively. Time to progression was 12.5 months, 4.7 months, 5.8 months, and 2.3 months, in Groups A, B, C, and D, respectively, and significantly longer in Group A compared with Group C, as well as in Group B compared with Group D. Median survival was 15.4 months, 9.1 months, 11.3 months, and 8.0 months in Groups A, B, C, and D, respectively, and significantly longer in Group B compared with Group D. Grade 3 or 4 non-hematological toxicity was not observed in Group A and B. HAI was effective for the control of unresectable colorectal liver metastasis and improved survival as second-line chemotherapy or more.     

Treatment for patients with liver metastasis from colorectal cancer--expansion of hepatic arterial infusion therapy

The treatment of patients with liver metastasis from colorectal cancer was evaluated. Although surgical resection was the most effective therapy and 5-year survival was 30%, more than two-thirds of the patients were judged unresectable at the beginning of the treatment. Those whose metastasis was judged to be unresectable received hepatic arterial infusion (HAI) of 5-FU therapy. In a comparison of the survival period, patients received more than 15 g of 5-FU were found to have a statistically significant longer survival than those who received less than 15 g. Even though the patients who revealed a PR or CR response with HAI did not survive more than 4 years, we began surgical resection in these patients after HAI therapy. As a result, the 5-year survival rate of patients whose metastasis was unresectable and who underwent surgical resection after successful HAI was 30% which was equal to the result of the patients judged resectable at the beginning of the treatment. Such treatment may become the fundamental treatment for unresectable liver metastasis in the near future.     

Prognostic significance of intrahepatic lymphatic invasion in patients with hepatic resection due to metastases from colorectal carcinoma

BACKGROUND: Intrahepatic spread from liver metastases of colorectal carcinoma has been well described; however, its prognostic value after hepatectomy is controversial. To clearly determine factors predicting survival after hepatectomy in such patients, the authors evaluated 14 clinicopathologic factors of liver metastasis from colorectal carcinoma with special reference to intrahepatic lymphatic invasion. METHODS: The authors retrospectively analyzed data obtained from 67 consecutive patients who underwent hepatectomy for liver metastasis from colorectal carcinoma. Intrahepatic spread was classified into discreet categories that were evaluated separately: invasion to the portal vein, hepatic vein, bile duct, and lymphatic or perineural space. Overall survival and disease free survival periods were examined as functions of clinicopathologic determinants by univariate and multivariate analyses. RESULTS: Intrahepatic spread was found in a total of 28 (43.1%) of the 65 evaluable cases. Portal vein invasion was found in 15 (23.1%) of these cases, hepatic vein invasion in 3 (4.6%), bile duct invasion in 10 (15.4%), and intrahepatic lymphatic invasion in 10 (15.4%). Five year overall and disease free survival rates after hepatectomy were 33.4% and 28.5%, respectively. A short interval (< 12 months) from treatment of primary colorectal carcinoma to liver metastasis and the presence of intrahepatic lymphatic invasion significantly and adversely affected the overall and disease free survival rates. CONCLUSIONS: Intrahepatic lymphatic invasion was shown statistically to be an independent predictor of recurrence and death after hepatectomy in patients with liver metastases from primary colorectal carcinoma.     

再次肝切除手术对结直肠癌肝转移复发患者的临床疗效和生存情况的影响因素

目的 探讨再次肝切除手术对结直肠癌肝转移复发患者的临床疗效和生存情况的影响因素.方法 回顾性分析94例结直肠癌肝转移复发患者临床相关资料,其中38例行再次肝切除术(观察组),其他56例进行内科化疗(对照组).结果 分别进行再次手术和化疗后,结直肠癌肝转移复发患者的1、3、5年生存率观察组为81.6%、52.6%和31.6%;对照组为62.5%、21.4%、7.1%,观察组患者生存率显著高于对照组(P<0.05).针对结直肠癌肝转移复发患者再次切除术的预后可能影响因素进行分析,其中癌直径大小、复发转移灶个数、切缘情况与患者5年生存率有关(P<0.05).术后并发症发生率为28.9%,均经过对症处理可耐受.结论 对于结直肠癌肝转移复发患者,再次肝切除术能提高远期疗效,对于癌直径较小、复发转移灶个数少、切缘阳性的患者效果更好.     

Surgical treatment for metastatic malignancies. Anatomical resection of liver metastasis: indications and outcomes

Hepatectomy may be the only treatment modality for the cure of colorectal liver metastasis. However, whether to perform nonanatomical resection or anatomical resection remains unclear. Original articles in English on liver metastasis, including reports that dealt with case series of more than 50 curative hepatectomies, were reviewed, and the current status of surgical treatment for colorectal liver metastasis was summarized, with a special emphasis on the relevance, indications, and outcomes of anatomical hepatectomy. Anatomical hepatic resection was performed in 63% of the patients. For patients who were treated by curative hepatectomy, including both anatomical and nonanatomical resection, the morbidity rates, mortality rates, 5-year survival rates, and rates of hepatic recurrence were 23%, 3.3%, 34%, and 41.2%, respectively. In 73 articles that each analyzed more than 50 patients treated with potentially curative hepatectomy, the incidence of anatomical resection exceeded 50% in 56 series, while anatomical resection was performed in fewer than 50% of the patients in 17 series. A comparison between these two groups naturally revealed a remarkable difference in the incidence of anatomical resection (72% versus 34%), but no difference in terms of morbidity; mortality; survival rates at 3, 5, and 10 years; or rate of hepatic recurrence. The profile of liver metastasis related to prognosis was generally advantageous to patients treated with nonanatomical resection, and this may have nullified the survival advantage of anatomical hepatectomy over nonanatomical resection. Anatomical resection provides a higher probability of coresecting microscopic invasions that are predictable but undetectable, and can be recommended as a standard procedure for locally advanced metastatic liver cancer.     

Results of hepatic arterial infusion chemotherapy with 5-FU and leucovorin for unresectable liver metastases from colorectal cancer

PURPOSE: Hepaticarterial infusional(HAI)5-FU chemotherapy, which involves the use of interventional radiology technique, has matured technically in Japan in the 1990's. The antitumor effect of 5-FU is enhanced by combination with leucovorin. This study was performed to evaluate the efficacy and toxicity of HAI 5-FU and leucovorin chemotherapy for patients with unresectable liver metastases from colorectal cancer. METHODS: Treatment was given to 20 patients with unresectable liver metastases from colorectal cancer. The chemotherapy regimen consisted of weekly HAI of 5-FU(1,000 mg/body)and leucovorin(250 mg/body)over five hours. The survival and response rates to the therapy were assessed according to RECIST. Hematologic and non-hematologic toxicity was assessed according to CTCAE v3.0. RESULTS: Combined HAI 5-FU and leucovorin therapy was carried out an average of 27 times. The response rate for liver tumors was 75%, and the median survival time was 22 months. The applied regimen caused only mild adverse events. There was no evidence of myelosuppression except for platelet decrease(grade 3)in a patient with chronic renal failure. CONCLUSION: This HAI approach using 5-FU and leucovorin was effective and the therapy for unresectable liver metastases from colorectal cancer was tolerated well. Therefore the HAI approach should be reconsidered as an effective therapy against this disease in Japan.     

A pilot study of multimodality therapy for initially unresectable liver metastases from colorectal carcinoma: hepatic resection after hepatic arterial infusion chemotherapy and portal embolization

The prognosis of patients with unresectable liver metastases is poor, even if hepatic arterial infusion chemotherapy (HAI) or systemic chemotherapy is administered. A pilot study was performed to evaluate the feasibility and efficacy of multimodality therapy with hepatectomy after HAI and portal embolization for such patients. Eight patients with colorectal carcinoma and synchronous unresectable liver metastases underwent resection of the primary tumor and placement of a pump, followed by HAI with 5-fluorouracil and mitomycin C. Owing to shrinkage of the liver metastases, two patients could undergo extended right hepatic lobectomy after portal embolization, which was deemed to be essential to prevent post-operative hepatic failure. The median survival time of the eight patients was 30 months, with a response rate of 75%. Complications including sclerosing cholangitis and duodenal ulcer were observed in five patients (63%). Additional hepatectomy could be performed successfully after portal embolization without morbidity in two patients. These two patients are still alive more than 6 years after initiation of HAI and have been free of disease for more than 5 years after hepatectomy. Hepatectomy after HAI and portal embolization is feasible and may be an option to cure selected patients with initially unresectable liver metastases.