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.     

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.     

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     

肝动脉药盒灌注氟脲苷联合全身化疗治疗不可切除老年结直肠癌肝转移

目的 探讨经肝动脉药盒灌注（HAI）氟脲苷（FUDR）联合全身化疗治疗不可切除老年结直肠癌肝转移患者的疗效及安全性.方法 对18例不可手术切除的老年结直肠癌肝转移回顾性分析.所有患者采用一种改进的介入方法植入肝动脉药盒,术后第2天开始接受HAI FUDR联合全身化疗.对治疗疗效、毒副反应及随访结果进行分析.结果 18例患者的总有效率为94.4%,其中完全缓解1例（5.6%）,部分缓解16例（88.9%）,疾病进展1例（5.6%）.8例患者转化为可手术切除,转化率为44.4%.中位无进展生存时间为26.0个月,中位总生存时间为30.2个月.结论 HAI FUDR联合全身化疗是治疗不可切除老年结直肠癌肝转移的一种安全有效的方法,可获得较高的手术切除率.     

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.     

Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5-fluorouracil

Most colorectal cancers metastatic to the liver are resistant to chemotherapy and are not amenable to surgical resection. This study evaluated our 6-year experience (July 1992-July 1998) in treating patients with unresectable hepatic colorectal metastases refractory to systemic 5-fluorouracil (5-FU). One hundred fifty-three patients underwent cryosurgical ablation (CSA) of 5-FU-resistant hepatic metastases. The patients then received either hepatic arterial floxuridine (FUDR), systemic CPT-11, or no postoperative adjuvant chemotherapy. Number, size, and location of hepatic metastases, carcinoembryonic antigen (CEA) levels, and type of postoperative treatment were analyzed. One to 15 lesions were frozen (median number, 3; median size, 6 cm), for a total of 73 synchronous and 80 metachronous lesions. Overall median survival was 28.4 months from the date of diagnosis of liver metastases and 16.1 months from the time of CSA. After cryosurgery alone, median survival was 13 months, which was significantly shorter than the post-CSA survival of 23.6 months with adjuvant CPT-11 and 21.2 months with hepatic FUDR (P = 0.007). Predictors of survival included preoperative CEA, postoperative reduction in CEA, and adjuvant chemotherapy (P < 0.05). Neither size, number of lesions, nor tumor location impacted survival. At a median follow-up of 13 months, 67% of patients have recurred (35% hepatic, 16% extrahepatic, and 49% both). Twenty percent of the recurrences were in the lobe of the CSA site. The 25 patients who underwent a second CSA had a median survival of 28.4 months from CSA and 40 months from the date of diagnosis of liver metastases. These data indicate that CSA offers an effective alternative for unresectable patients resistant to 5-FU. Systemic CPT-11 or regional FUDR may further prolong survival after CSA.     

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.     

Alternating hepatic arterial infusion and systemic chemotherapy for liver metastases from colorectal cancer: a phase II trial using intermittent percutaneous hepatic arterial access.

PURPOSE: To evaluate the objective response to a short course of hepatic arterial infusion (HAI) using temporary, percutaneously placed catheters alternating with systemic prolonged continuous infusion fluorouracil (ci 5-FU) and daily oral leucovorin (L). PATIENTS AND METHODS: Eligible patients were previously untreated (except for adjuvant therapy) adults with liver-predominant metastases, with Eastern Cooperative Oncology Group performance status of 0 to 2. Treatment regimen included HAI with fluorodeoxyuridine (FUDR) 60 mg/m2/d and L 15 mg/m2/d continuously infused daily for 4 days. After a 1-week rest, ci 5-FU was administered through a central venous access device using a dose of 180 mg/m2/d with a fixed dose of oral L at 5 mg/m2/d for 21 out of 28 days. Cycles were repeated every 6 weeks. After four cycles of therapy, patients were maintained on ci 5-FU and daily oral L until evidence of progression. RESULTS: Forty-three patients were enrolled onto this trial. One patient was ineligible. The objective response rate for all patients (17 partial, zero complete) was 41% (95% confidence interval [CI], 26% to 56%). Five patients were not able to receive at least one complete cycle of HAI. Among patients who received at least one complete cycle of HAI, the response rate was 46% (95% CI, 30% to 62%). Five patients underwent a liver resection after enrolling onto the protocol. At the time of analysis, estimated median time to progression was 6 months, and estimated median overall survival was 13 months. CONCLUSION: The objective response rate was comparable to that achieved with more prolonged and more frequent HAI using FUDR. This approach should be studied as an acceptable alternative to surgically placed hepatic arterial catheters/pumps and may have a role as neoadjuvant therapy for liver metastases that are unresectable, as well as an adjuvant role for patients with resected hepatic metastatic colorectal cancer.     

Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma.

PURPOSE: To assess the efficacy and tolerability of three treatments for patients with documented adenocarcinoma of the colon and/or rectum who have undergone complete resection of primary tumor and have nonresectable liver metastases that do not exceed 75% of the liver volume. PATIENTS AND METHODS: A total of 168 patients at 25 treatment centers were enrolled onto this prospective, multicenter, randomized study. The three treatment arms were as follows: (1) fluorouracil (5-FU)/leucovorin (LV) administered via hepatic arterial infusion (HAI), (2) 5-FU/LV administered via intravenous (IV) infusion, and (3) fluorodeoxyuridine (FUDR) administered via HAI. RESULTS: Median times to disease progression for the three treatment arms were as follows: 9.2 months for patients treated with HAI 5-FU/LV, 6.6 months for IV 5-FU/LV, and 5.9 months for HAI FUDR. Median survival times for patients treated with HAI 5-FU/LV, IV 5-FU/LV, and HAI FUDR were 18.7 months, 17.6 months, and 12.7 months, respectively. There was a nearly two-fold increase in time to progression in addition to a survival benefit among patients with an intrahepatic tumor burden of less than 25% who were treated with HAI 5-FU/LV. The most common adverse events were stomatitis, nausea and vomiting, skin irritation, diarrhea, and elevated serum levels of liver enzymes. Some patients exhibited severe reactions, including biliary sclerosis and chemical hepatitis. CONCLUSION: Although the use of HAI 5-FU/LV as a means of treating liver metastases after resection of colorectal carcinoma warrants further investigation, it cannot be recommended as a routine therapeutic measure at this time.     

A case of multiple liver metastases from rectal cancer in poor performance status successfully treated with hepatic arterial infusion chemotherapy plus CPT-11

Hepatic arterial infusion (HAI) chemotherapy is one of the strategies for cases in poor performance status. This is a case report of multiple liver metastases from rectal cancer in poor performance status successfully treated with HAI plus CPT-11. A 59-year-old man who had rectal cancer, multiple liver metastases and para-aortic LN metastasis underwent a laparoscopic rectal anterior resection. He denied receiving postoperative chemotherapy and selected alternative therapy at another clinic. Four months later, he visited our hospital. His liver metastasis and performance status got worse, so HAI of 5-FU 1250 mg/m2 for 5-hour weekly (weekly high-dose 5-FU: WHF) was started at first. After 3 courses, his status improved, so systemic chemotherapy was added. HAI (WHF: 1000 mg/m2) plus CPT-11 (100 mg/m2) was effective, and liver metastases showed a significant reduction (PR) on abdominal CT. HAI plus CPT-11 was effective for a patient of the poor performance status with unresectable liver metastasis.     

Phase I/II study of irinotecan, UFT and leucovorin with hepatic arterial infusion using 5-FU in colorectal cancer patients with unresectable liver metastases

Purpose

To evaluate the efficacy and tolerability of systemic chemotherapy with irinotecan (CPT-11), UFT and leucovorin (LV) combined with hepatic arterial infusion (HAI) consisting of 5-fluorouracil (5-FU) in colorectal cancer patients with unresectable liver metastases.

Methods

Patients were treated concurrently with escalating doses of intravenous CPT-11 (100, 120, and 140?mg/m²) on day 1 of each 14-day treatment cycle, with oral UFT (300?mg/m² per day) and LV (75?mg/body per day) on days 1?C7 of each cycle, and with HAI 5-FU (2,000?mg/week) on days 8?C14 of each cycle.

Results

Twelve patients were enrolled in the phase I study. The maximum-tolerated dose was not reached. Consequently, the recommended dose of CPT-11 for the phase II study was determined to be 140?mg/m². Twenty-two patients were evaluated in the phase II study. Five patients experienced grade 3 neutropenia, two experienced grade 3 anorexia, two experienced nausea, and two experienced vomiting. An overall response was observed in 19 out of 22 patients (86.4%). The median progression-free survival period was 11.2?months, and the 3-year survival rate was 50.6%. Fourteen patients (63.6%) were ultimately able to undergo a complete liver resection.

Conclusions

Chemotherapy with CPT-11 and UFT/LV combined with HAI yielded a high response rate and enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. Further trials are warranted.     

Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer

Background: The purpose of the study was to determine the maximum tolerated dose of systemic oxaliplatin (oxal), 5-fluorouracil (5-FU) and leucovorin (LV) that could be administered with hepatic arterial infusion (HAI) of floxuridine (FUDR) and dexamethasone (Dex) in the adjuvant setting after hepatic resection.Methods: Thirty-five patients with resected liver metastases were entered into a phase I trial using HAI FUDR/Dex with escalating doses of oxal and 5-FU.Results: The initial dose of HAI FUDR was fixed at 0.12 mg/kg × pump volume divided by pump flow rate plus Dex infused over the first 2 weeks of a 5-week cycle. Systemic chemotherapy was delivered on days 15 and 29 with the doses of oxal escalated from 85 to 100 mg/m² and the 5-FU 48-h continuous infusion doses from 1000 to 2000 mg/m². The LV dose was fixed at 400 mg/m². Dose-limiting toxic effects were diarrhea, 8.5%, and elevated bilirubin, 8.5%. With a median follow-up of 43 months, the 4-year survival and progression-free survival were 88% and 50%, respectively.Conclusions: Adjuvant therapy after liver resection with HAI FUDR/Dex plus systemic oxal at 85 mg/m² and 5-FU by continuous infusion at 2000 g/m² with LV at 400 mg/m² is feasible and appears effective. Randomized studies comparing this regimen to systemic FOLFOX are suggested.     

Hepatic artery infusion of chemotherapy as a treatment for hepatic metastases from colorectal cancer

Hepatic artery infusion (HAI) of chemotherapy as a treatment for hepatic metastases from colorectal cancer has become more commonly used after the introduction of the totally implantable hepatic artery pump in the early 1970s. Floxuridine (FUDR) is the generally used chemotherapy agent in the pump because of its high solubility and high extraction rates by the liver on the first pass of the chemotherapy through the hepatic circulation. HAI has been used mainly to treat unresectable liver metastases in patients who have liver metastases only. The other scenario for pump use has been as an adjuvant therapy after resection of all metastatic disease inthe liver. The rationale for HAI includes the unique dual blood supply of the liver allowing chemotherapy given into the artery and sparing the normal cells, which get their predominant blood supply from the portal vein. The details of pump design will be reviewed. Complications from HAI are specific for this therapy and will be reviewed. Treatment of unresectable liver metastases with HAI has been the subject of a number of prospective randomized studies. These will be presented, along with newer phase II studies. Three randomized studies on the usefulness of HAI after hepatic resection will be presented.     

Systemic chemotherapy for advanced colorectal cancer with liver metastasis

We report the progress of systemic chemotherapy for advanced colorectal cancer with liver metastasis. It must be noted that the purpose of this treatment is to prolong the symptom-free period. Review of hepatic arterial infusion (HAI) compared with systemic chemotherapy for the treatment of unresectable liver metastases from colorectal cancer showed that was attained with HAI a much higher response rate and survival benefit than systemic chemotherapy. However, systemic chemotherapy has shown progress since that time. Regarding administration methods, continuous injection is better than bolus injection for 5-FU. New modulators of 5-FU have also became available, such as leucovorin, CPT-11, and I-OHP. Futhermore, many studies of 5-FU-based combination therapy have shown that the mean survival time (MST) and response rate (RR) are now close to those of HAI. Finally, the combination with HAI with systemic chemotherapy using CPT-11 resulted in the highest RR of 74%. Further trials of such combination therapy will be performed in the future.     

Extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion--a case report

A 72-year-old woman, who had the carcinoma of cecum with unresectable multiple liver metastases, underwent ileocecal resection and insertion of hepatic arterial infusion catheter. Hepatic arterial infusion (HAI) chemotherapy using Leucovorin. 5-FU caused to decrease liver metastases after an initiation of HAI. However, the metastatic nodule at the right lobe of lung was found. Then systemic chemotherapy with CPT-11 CDDP was performed alternately with HAI chemotherapy. After the initiation of revised regimen, all metastatic lesions were shrunk. We here in present the case of extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion.     

Extent of hepatic resection does not correlate with toxicity following adjuvant chemotherapy

BACKGROUND: In patients with liver metastases from colorectal cancer, survival can be increased by hepatic resection. Treatment with hepatic arterial infusion (HAI) and systemic chemotherapy following resection may further increase survival and decrease recurrence, but may also result in hepatic and systemic toxicity. This article will address the question of whether large hepatic resections resulting in a greater loss of healthy liver predisposes patients to developing toxicity from the subsequent chemotherapeutic regimens. DESIGN: Retrospective analysis of 88 patients who underwent liver resection of colorectal metastases followed by adjuvant HAI and systemic chemotherapy and whose computerized tomography (CT) scans were done at Memorial Sloan-Kettering Cancer Center (MSKCC). Liver volumes were calculated from CT scans and used to determine the percentage change in healthy liver volume between the pre- and post-operative CT scans. Hepatic and systemic toxicities were defined according to the Common Toxicity Criteria of the National Cancer Institute. RESULTS: Patients experienced a mean percentage decrease in healthy liver tissue of 17% (range: 57% decrease to 32% increase) at an estimated 1 month after resection and at the initiation of chemotherapy. In a logistic regression model using percentage change in the healthy liver volume as a continuous variable, no significant association was revealed between percentage of healthy liver resected and diarrhea (P = 0.47), leukopenia (P = 0.37), neutropenia (P = 0.31), high bilirubin (P = 0.27), or alkaline phosphatase (P = 0.79). CONCLUSIONS: A greater loss of healthy liver following resection of hepatic metastases from colorectal cancer does not seem to predispose to the development of toxicity from adjuvant HAI and systemic chemotherapy.     

Chemotherapy for liver metastasis of colorectal cancer

In colorectal cancer, liver metastasis is the most common and most important prognostic factor. Although surgical resection is the first choice of treatment for liver metastasis of colorectal cancer, there are many cases we cannot choose the surgical treatment. The chemotherapy is very important in such cases. We examined 18 cases of unresectable liver metastases from colorectal cancer which were adapted a hepatic arterial infusion of 5-FU (HAI) with a weekly high-dose infusion method (WHF) as the first-line treatment, and then systemic chemotherapy of CPT-11 in combination with 5-FU as the second-line treatment. The response rate of this treatment is 72% (13/18) and the 1-, 2-, 3-year survival rates were 100% (16/16), 83% (10/12), and 50% (5/10), respectively. The combination chemotherapy of HAI with systemic chemotherapy using CPT-11 seemed to be an effective treatment method.     

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.