A case of colon cancer with multiple liver metastases effectively treated with hepatic arterial infusion followed by systemic chemotherapy

A 63-year-old female was diagnosed as descending colon cancer with severe liver dysfunction caused by multiple liver metastases. Her performance status (PS) was 3 because of liver dysfunction and high fever. Initially, hepatic arterial infusion (HAI) chemotherapy was started to reduce the size of metastatic tumors and to prevent a liver failure. After 10 courses of HAI chemotherapy, she recovered from liver dysfunction, and CapeOX plus bevacizumab regimen was started. A partial response of metastatic liver tumors was observed after 8 cycles of this regimen and metastatic lung tumors were disappeared. The patient was alive after 12 months with PS 0 and CapeOX was continued.     

A case of elderly advanced gastric cancer patient with multiple liver metastases effectively treated by hepatic arterial infusion chemotherapy

An 85 years old man was performed systemic chemotherapy after the palliative gastrectomy for unresectable gastric cancer with multiple liver metastases. The response evaluation revealed a progressive disease after 4 courses of first-line S-1 therapy and 3 courses of second-line paclitaxel therapy. At this point, metastatic lesions were still localized in the liver, so hepatic arterial infusion chemotherapy (HAI) was introduced as third-line therapy. Despite the marked reduction of all target lesions and reduced tumor marker level after 25 weeks of HAI without any adverse event, novel multiple metastatic lesions had appeared in the lung and celiac LNs, resulted in the cessation of HAI. Then he had suffered grade 3 mucositis oral and anorexia throughout 2 courses of fourth-line S-1 + CDDP therapy and fifth-line docetaxel therapy. Considering that the goal of treatment for unresectable gastric cancer patients is to delay developing symptoms and to prolong their life with the least adverse event, HAI could be an effective therapy.     

Evaluation of hepatic arterial infusion chemotherapy with low-dose leucovorin and 5-FU from reservoir for multiple liver metastases by colorectal cancer

5 patients with colorectal cancer with multiple liver metastases underwent resection of primary lesions. We then evaluated the effects of hepatic arterial infusion chemotherapy with low-dose leucovorin and 5-FU. Weekly, dl-leucovorin of 30 mg/body or l-leucovorin of 25 mg/body was administered as a bolus, then 5-FU of 500 mg/body was administered for 1 hour through the hepatic artery from the subcutaneous reservoir on an outpatient basis. 2 of 5 patients achieved a CR of liver metastases, but later 1 of these 2 cases had metastases of bone and lung. No adverse effects, such as nausea, vomiting, diarrhea or bone marrow suppression, were seen after this treatment in any of the patients.     

Hepatic arterial infusion of low-dose leucovorin/5-FU chemotherapy for unresectable hepatic metastases from colorectal cancer

Hepatic arterial infusion (HAI) chemotherapy for unresectable liver metastases from colorectal cancer (CRC) is generally indicated to patients without extrahepatic lesions. This study was performed to examine whether or not it was possible to obtain a comparable survival time, response rate (RR) and modest toxicity combining low-dose LV and 5-FU (LV/5-FU) with HAI for the patients with unresectable liver metastases from CRC. Twenty two patients with unresectable multiple liver metastases were enrolled in the study. These were patients who had been admitted from 1994 to 2003 in our hospital. Patients were given LV at 25 mg/body immediately followed by 5-FU at 500 mg/body as a 2-hour HAI daily for 5 consecutive days every 5 weeks. The median survival time (MST) of HAI patients was 24.5 months. According to the treatment in the HAI patients, one patient was CR, 6 were PR, 9 were NC, 6 were PD, and the response rate (RR) was 31.8% (7 of 22 patients). The toxicities to this regimen on HAI were observed in 12 patients, and grades 3 or 4 were in 3 patients only. These results suggested that HAI with LV/5-FU can be useful for unresectable liver metastases from CRC.     

A case of advanced gastric cancer effectively treated with combination of weekly paclitaxel and hepatic arterial infusion of 5-FU/LV

The patient was a 66-year-old woman who underwent upper gastrointestinal endoscopy as part of a detailed examination because of loss of appetite and anemia, and type 2 gastric cancer was detected on the greater curvature in the pyloric area. Abdominal ultrasonography and CT revealed lymph node enlargement around the pyloric area and multiple liver metastases in both lobes of the liver. Curative resection was judged to be impossible, and oral S-1 therapy was started. However, no efficacy was observed even after the completion of three courses, and especially because of the rapid increase in the size of the liver metastases, treatment was switched to combination therapy consisting of a continuous hepatic artery infusion of 5-FU+Leucovorin (day 1-7) and weekly PTX for 3 consecutive weeks (day 8, 15, 22) followed by a 1-week rest. The tumor marker levels decreased rapidly, and at the end of 4 courses marked regression of the primary tumor and lymph node metastases as well as of the metastatic foci in the liver was observed. Adverse events have been mild, and at present, 6 months after the switch in treatment, good QOL has been maintained, and treatment is continuing. This method appears to be an effective treatment strategy for unresectable advanced gastric cancer complicated by liver metastasis.     

A case of postoperative pelvic metastasis and multiple liver metastases of the rectal cancer successfully treated by arterial infusion therapy with 5-FU/leucovorin

A 55-year-old man underwent a rectal amputation for rectal cancer in 1994. As the tumor marker was elevated in 2002, we performed an abdominal CT scan and detected local and multiple liver recurrences. We treated the patient with intra-arterial infusion of 5-FU/LV via the internal iliac artery and the hepatic artery. The chemotherapy was performed on a weekly basis; it consisted of 5-FU (500 mg/body), administered for 5 hours to bilateral reservoirs through an infusion pump and l-leucovorin (400 mg/body), administered intravenously for 2 hours. After 18 administrations of this regimen during a hospital stay and after a discharge from the hospital as an outpatient, the multiple liver metastases that were observed have disappeared. Further, the local recurrences showed a partial reduction in tumor size with a decrease in perineal pain. Subsequently, the patient did not require further doses of morphine. He exhibited no severe side effects except for grade 1 nausea, and his QOL was also good. Therefore, local intra-arterial infusion chemotherapy with 5-FU/LV appears to have been effective for rectal cancer recurrences.     

A case of gastric cancer with multiple liver metastases effectively treated by hepatic arterial infusion of MMC, TS-1/CDDP therapy, and thermotherapy

A 62-year-old man was revealed to have type 2 gastric cancer with synchronous liver metastasis. We considered liver metastasis to be a prognostic factor, and performed two courses of combination thermochemotherapy consisting of hepatic arterial infusion of MMC and TS-1 and thermotherapy. Partial response was observed in the liver metastases,but the primary lesion showed no changes; therefore, we performed four courses of combination thermochemotherapy consisting of TS-1/CDDP therapy and thermotherapy. By the end of three courses of this therapy,the primary lesion had cicatrized,and endoscopic biopsy revealed no cancer cells. These results suggest that gastric cancer,in which liver metastasis is considered to be a prognostic factor,can be effectively treated by combination therapy with hepatic arterial infusion therapy, followed by thermochemotherapy for the primary lesion.     

Method of levofolinate.5-FU administration by hepatic arterial infusion therapy for hepatic metastasis from colorectal cancer

Hepatic arterial infusion chemotherapy with levofolinate (l-leucovorin) and fluorouracil regimen was performed using an implanted port system on unresectable hepatic metastasis patients with colorectal cancer. A comparative study was performed on two groups in which the levofolinate was administered arterially or intravenously. Levofolinate 200-250 mg/m(2) was infused for two hours intra-arterially or intravenously, and 5-FU 400-600 mg/m(2) was administered as a bolus in midinfusion. The regimen was repeated weekly for six weeks, followed by no medication for two weeks. Six patients were administered intra-arterially and 7 patients intravenously. The response rate was higher in the group in which levofolinate was given intravenously. The adverse effect was lower in the former than in the latter group. When 5-FU and levofolinate was performed using an implanted port system, it seemed better to administer levofolinate intravenously.     

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.     

Five-hour hepatic arterial infusion of high-dose 5-FU on weekly schedule for liver metastases from colorectal cancer

The study of 5-hour hepatic arterial infusion of high-dose 5-FU on a weekly schedule (weekly high-dose 5-FU HAI: WHF) was conducted to reveal a new pump-free regimen to avoid the reduction of QOL due to continuous infusion pumps. By the phase I study, the recommended dose was determined to be 1.000 mg/m2/5 hrs qw. Thus far, 20 cases entered the phase II study of this regimen, and 1 CR and 10 PRs were observed in 15 evaluated cases without major toxicity. This regimen is highly effective for liver metastases from colorectal cancer without reduction of QOL in patients by pumps. A study of this regimen involving a large number of cases is required.     

A case report of complete remission of liver metastases from colorectal cancer treated with continuous hepatic arterial infusion

We encountered a patient with liver metastases from colorectal cancer in whom continuous hepatic arterial infusion brought complete remission. A 58-year-old man was admitted to our hospital for advanced rectal cancer with multiple liver metastases. He underwent a low anterior resection (D2). Continuous hepatic arterial infusion of 5-FU (250 mg/day) with a weekly arterial infusion of MMC (4 mg) was performed for 14 days. Six continuous hepatic arterial infusions resulted in a complete remission. The patient has been free from any sign of recurrence for 37 months after the operation. Continuous hepatic arterial infusion using 5-FU and MMC seems to be effective in the treatment of multiple liver metastases from colorectal cancer.     

Evaluation of hepatic arterial infusion chemotherapy with levofolinate (l-LV) and 5-fluorouracil (5-FU) for multiple liver metastases from colorectal cancer

We evaluated the effect of hepatic arterial infusion chemotherapy with levofolinate (l-LV) and 5-fluorouracil (5-FU) for multiple liver metastases from colorectal cancer. All patients received drugs on an outpatient basis every six weeks, followed by no medication for two weeks. In this regimen levofolinate (200 mg/m2) was administered for two hours and 5-fluorouracil (500 mg/m2) was administered for thirty minutes as a bolus. A complete response was obtained in five patients and a partial response in five patients; the overall response rate was 40%. All patients could receive this therapy on an outpatient basis because no patient had side effects of Grade 3 or over. It is suggested that our protocol may be useful for improvement of outcome.     

A case of unresectable multiple hepatic metastases from colorectal cancer successfully treated with panitumumab therapy on third-line

In a patient with multiple liver metastases of colorectal cancer in whom tumor response had been achieved by 5-FU hepatic arterial infusion, the catheter for arterial infusion chemotherapy was occluded resulting in re-elevation of tumor marker levels. Second-line IRIS therapy using S-1 and CPT-11 was started. IRIS therapy reduced tumor marker levels to a degree greater than that previously achieved with 5-FU hepatic arterial infusion, and diagnostic imaging allowed a judgment of partial response. But tumor marker levels increased gradually. After all, diagnostic imaging allowed a judgment of progressive disease and an eminent elevation of tumor marker levels in one year. Third-line panitumumab therapy was started. Panitumumab therapy reduced tumor marker levels to a degree greater than that previously achieved with 5-FU hepatic arterial infusion and IRIS therapy, and diagnostic imaging allowed a judgment of partial response. We report herein a successful case. Hepatic arterial infusion therapy is one of the treatment methods characterized by a lower incidence of adverse reactions, relatively low cost, and expectation of high anti-tumor efficacy as compared to chemotherapy such as FOLFIRI. IRIS therapy does not require a port insertion and pump carrying, and its cost is about half of FOLFIRI therapy. When used as second-line therapy for unresectable colorectal cancer, non-inferiority of IRIS therapy to FOLFIRI therapy has been demonstrated in a phase II/III clinica (l FIRIS) study. We may say that IRIS therapy is promising as an equivalent to hepatic arterial infusion therapy in the treatment of liver metastases of colorectal cancer. In addition, we may say that panitumumab therapy is promising as an equivalent to hepatic arterial infusion therapy and IRIS therapy.     

A case of intrahepatic cholangiocarcinoma effectively treated by hepatic arterial infusion chemotherapy

The patient was a 50-year-old woman who suffered from gastric discomfort. She was first diagnosed as intrahepatic cholangiocarcinoma with hepatic, paraaortic lymphnodal and bone metastasis. Initial systemic chemotherapy using gemcitabine (GEM) and 5-FU failed to control the disease activity. Then she was given GEM and cisplatin (CDDP) combination chemotherapy. The response was assessed as stable disease (SD), but grade 4 leukopenia was seen. Then systemic therapy using GEM, and hepatic arterial infusion therapy with CDDP, l-leucovorin and 5-FU were continued biweekly. Partial response (PR) was achieved six months later, and her disease status was maintained as SD. This hepatic arterial infusion chemotherapy would be safe and feasible as therapy for inoperable intrahepatic cholangiocarcinoma.     

A case of AFP-producing gastric cancer after curative operation effectively treated with chemotherapies including hepatic arterial infusion therapy

A 63-year-old woman was admitted complaining of epigastralgia. An endoscopic examination revealed a Borrmann type 2 lesion at the greater curvature of the middle third in the stomach. Abdominal computed tomography detected no liver metastasis. The preoperative serum alpha-phetoprotein (AFP) level was elevated to 242.9 ng/ml. 5-fluorouracil (5-FU) was given 200 mg/day for 26 days orally. Distal gastrectomy with D3+ No. 16b1 lymph node dissection, cholecystectomy and hepatic arterial canulation were performed, and mitomycin C 20 mg was injected intravenously during the operation. Immunohistochemical staining of the specimen for AFP by the SAB method was positive in the cancer lesion. After the operation, FP (cisplatin 100 mg on day 1, 5-FU 750 mg on days 1-3) therapy of one course and intrahepatic arterial infusion therapy using adriamycin 10-20 mg every 2 weeks for 7 months were conducted. Moreover, the patient took UFT 400 mg/day for 26 months orally on an outpatient basis as an adjuvant chemotherapy. The only toxicity was neutropenia (grade 3), but it abated without an interruption in the chemotherapy. The AFP level declined gradually, and returned to the normal range 1 month after surgery. The patient is still alive with no sign of hepatic metastasis or recurrence 7 years and 7 months after the gastrectomy.     

A case of successfully treated unresectable multiple liver metastases from colon cancer by hepatic arterial infusion chemotherapy and systemic chemotherapy

Sigmoidectomy was performed for a 69-year-old man with sigmoid colon cancer and unresectable multiple liver metastases. The histological diagnosis was undifferentiated carcinoma of sigmoid colon. Hepatic arterial infusion chemotherapy with 5 FU and systemic chemotherapy with CPT-11 were performed after the operation. A complete response (CR) was achieved for liver metastases. The recurrent sign was not found at 23 months after the operation. This combination therapy is expected to be an alternative treatment of colorectal cancer with unresectable multiple liver metastases.     

A case of postoperative liver metastases from gastric cancer successfully treated with hepatic arterial infusion of paclitaxel

A 69-year-old man underwent total gastrectomy for advanced gastric cancer in August 2001. After surgery, he was treated daily with UFT 300 mg. In October 2002, the tumor marker (CEA) increased in value, and CT revealed multiple liver metastases. Because there were no extrahepatic metastases, we attempted to use hepatic arterial injection chemotherapy. A reservoir was placed in the hepatic artery on November 12. Thereafter, intra-arterial injection of paclitaxel at 120 mg (80 mg/m2) was administered over one hour to the reservoir. This arterial injection chemotherapy was administered once weekly for 3 weeks followed by 1 week rest. After 3 courses, CEA decreased markedly and CT revealed remarkable tumor reduction which was thought to show a partial response (PR). After 6 courses, PR was continued. Adverse effects were only grade 1 alopecia and leukopenia. No major adverse effects were observed. These results suggest that hepatic arterial injection therapy with weekly paclitaxel is effective against recurrent gastric cancer with liver metastases.     

Extensive liver metastasis of gastric cancer effectively treated by hepatic arterial infusion of 5-fluorouracil/cisplatin

Most gastric cancer patients with jaundice caused by extensive liver metastasis show no tumor shrinkage response to systemic chemotherapy, while often showing severe adverse reactions. Their prognosis is very poor. We experienced two patients for whom hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) and cisplatin through an implantable port was effective for treating extensive liver metastasis. One patient had jaundice (serum bilirubin level before HAI therapy, 12.4 mg/dl) caused by metachronous liver metastasis, and prior systemic chemotherapy with 5-FU and irinotecan had not been effective. The other patient had gastric cancer with synchronous liver metastasis and also exhibited jaundice (serum bilirubin level before HAI therapy, 11.8 mg/dl). Both patients were treated with HAI of cisplatin, 20 mg/m ² for 30 min on day 1, and continuous intraarterial infusion of 5-FU, 300 mg/m ² , from day 1 to day 4 every week. Their metastatic liver tumors were significantly reduced in volume and the jaundice disappeared. They survived for 30 and 27 weeks, respectively. A pharmacokinetic study conducted during the period of partial remission revealed that the extraction ratios of 5-FU and cisplatin in the liver were 0.89 and 0.024, respectively, suggesting a favorable first-pass effect of 5-FU. Although our findings here suggest that the successful local control of liver metastasis could improve the deteriorated condition and prolong the survival in some patients with far advanced cancer, it is essential to pay much attention to possible adverse effects during the treatment. Received: April 17, 2000 / Accepted: July 12, 2000     

A case of postoperative multiple hepatic metastasis from gastric cancer successfully treated by percutaneous microwave coagulation therapy and hepatic arterial infusion chemotherapy

A 61-year-old male who underwent radical resection for gastric cancer was diagnosed with multiple hepatic metastasis 2 years and 2 months after the surgery. He first underwent percutaneous microwave hepatic coagulation therapy with segmental hepatic blood flow occlusion and obtained complete coagulation of the main tumor. Consecutively, he received hepatic arterial infusion chemotherapy (FAP: 5-FU, cisplatin, adriamycin) against residual multiple hepatic tumors. These hepatic recurrent lesions disappeared completely after 3 sessions of arterial infusion chemotherapy. At present, this patient is alive with no recurrent lesions, 1 year and 6 months from the beginning of treatment for hepatic metastasis. Recently, we tried hepatic arterial infusion chemotherapy (FAP) in four cases in which the recurrence from gastric cancer was not only in the liver but elsewhere. The response rate (CR and PR) was 75% and no major side effects were observed. In conclusion, some cases can obtain longer survival if the multimoderate therapy including hepatic arterial infusion chemotherapy (FAP) and microwave coagulation therapy are effective.     

Clinical outcome of intra-hepatic arterial infusion therapy for multiple liver metastases from colorectal cancer

Weekly infusion of high-dose 5-FU through the hepatic artery after resection of colorectal cancer was compared with resection alone in patients with multiple liver metastases. Twenty-seven patients (Group I) underwent hepatic artery infusion chemotherapy and 74 patients (Group II) underwent resection alone. The average survival time was 17.9 months in Group I and 8.5 months in Group II. One CR and 7 PR were achieved with arterial infusion therapy and the response rate was 29.6%. One- to three-year survivals were better in Group I than Group II.