A case of gastric cancer with liver metastases successfully treated with combination therapy of systemic and hepatic arterial infusion chemotherapy

A 67-year-old man was admitted to our hospital because of advanced gastric cancer associated with metastases to the liver, the lymph nodes along the lesser curvature and the infradiaphragmatic lymph nodes. As we considered the primary lesion and the liver metastases to be unresectable, we treated him with combination therapy of systemic and hepatic arterial infusion chemotherapy. The regimen of systemic chemotherapy consisted of cisplatin (CDDP) and UFT. Hepatic arterial infusion chemotherapy included 5-fluorouracil (5-FU), doxorubicin (DXR) and mitomycin C (MMC). We repeated this therapy six times. The size of the primary lesion and the lymph node metastases decreased significantly after the chemotherapy. The size of the liver metastases did not change, but they appeared to necrotize. The patient maintained a good quality of life during the therapy. He finally died of peritonitis carcinomatosa 18 months after the diagnosis. This case indicated that combination therapy of systemic and hepatic arterial infusion chemotherapy was effective in cases of unresectable gastric cancer associated with liver metastases.     

A case of the 5-year survivor of ascending colon cancer associated with synchronous multiple liver metastasis and peritoneal dissemination successfully treated with combination therapy of systemic and hepatic arterial infusion chemotherapy

A 67-year-old woman was diagnosed by a series of examinations as having ascending colon cancer with synchronous multiple liver metastasis. She underwent an operation after the PTPE (percutaneous transhepatic portal vein embolization) to the right lobe of the liver, as we considered that the metastatic liver tumors were all resectable. In the surgery, we identified seven peritoneal tumors and a lymph node swelling. We then pathologically diagnosed them as being peritoneal dissemination (p3) and lymph node metastasis (n2(+)). Therefore, hepatectomy was not performed, but the right hemicolectomy (D2) and insertion of an arterial infusion catheter into the hepatic artery were performed. In addition, all seven peritoneal tumors were resected. After being discharged from hospital, she was treated as an outpatient with the combination chemotherapy of systemic intravenous administration (5-fluorouracil or 5-FU, 2,500 mg/month) and hepatic arterial infusion (5-FU, 1,500 mg/week) for 16 months. Then, she continued to take tegafur uracil (300 mg/day) by mouth for 39 months. The metastatic liver tumors were gradually reduced and resulted in complete response (CR) for 20 months after the operation. She has been in remission for the past 5 years without recurrence. During the treatment, we noticed a complete atrophy that was sustained in the right lobe of the liver to which PTPE was performed. As far as hepatic arterial infusion chemotherapy is concerned, our case study was interesting and effective.     

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.     

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.     

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.     

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.     

A case of liver metastases of breast cancer successfully treated by combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab

A 43-year-old woman underwent breast-conserving therapy for right breast cancer with multiple liver metastases (pT3N3aM1, stage IV, ER (-), PgR (-), HER2 (3+)), in November, 2002. Following surgery, she received combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab weekly. During therapy, no serious side effects and only grade 1 nausea were observed; after 3 courses, therapy was safely continued on an outpatient basis. Metastatic liver tumors responded to the treatment, and they completely disappeared on an abdominal CT 5 months later. In addition, all elevated tumor markers in serum decreased to the normal range. No new metastatic or recurrent lesions were found 14 months after surgery. We conclude that this combination chemotherapy is safe and may be very useful for the treatment of breast cancer patients with liver metastasis.     

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.     

Five-year survivor with liver metastasis from gastric cancer successfully treated with systemic chemotherapy

We report a patient with liver metastasis from gastric cancer who has achieved a 5-year survival after systemic chemotherapy. The patient was diagnosed with advanced gastric cancer and received a total gastrectomy in August 1991, followed by adjuvant chemotherapy. Liver and lymph node metastases were detected in April 1994, and systemic chemotherapy with a combination of etoposide, doxorubicin, and cisplatin was initiated. Although the liver metastasis completely disappeared, lymph node metastasis at the falciform ligament of the liver and around the portal fissure remained after six courses of this therapy. A second type of chemotherapy, a combination of 5-fluorouracil and methotrexate, was then administered, 12 times, from December 1994 to May 1995, during which time no disease progression was observed. After surgery for the metastatic lymph nodes in August 1995, no progression was observed until December 1998, when a tumor thrombus was detected in the portal vein. Combination chemotherapy of irinotecan and cisplatin was initiated in January 1999. Although tumor regression was achieved after two courses of this, the disease continued to progress after five courses. In July 1999, a fourth type of chemotherapy, using 1 M tegafur-0.4 M gimestat-1 M otastat potassium (S-1), was initiated, and size reduction of the tumor thrombus was achieved; this therapy has continued to the time of submission of this report. Received: April 3, 2000 / Accepted: June 27, 2000     

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.     

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

The patient was a 67-year-old man who had been operated for eshophageal cancer 4 years ago. He was diagnosed as intrahepatic cholangiocarcinoma by CT after 2 years of the operation. After admission to our hospital, he was treated by hepatic arterial infusion chemotherapy with CDDP, levofolinate calcium (L-LV) and 5-FU with chronomodulation. After a few more months of the treatment, abdominal CT revealed that the size of hepatic tumor decreased remarkably. There were no side effects without bone marrow suppression (grade 1). It seemed that hepatic arterial infusion chemotherapy with chronomodulation may be an effective strategy against intrahepatic cholangiocarcinoma in high risk case.     

A case of postoperative multiple hepatic metastasis from esophageal cancer successfully treated by surgical resection and hepatic arterial infusion chemotherapy]

A 66-year-old male who underwent radical resection for esophageal cancer (stage IV) was diagnosed with multiple hepatic metastasis 1 year and 3 months after the surgery. He underwent hepatic resection and received systemic chemotherapy (FAP: 5-FU, ADR, CDDP), as the post-operative adjuvant therapy. One year and 3 months later, there was a huge recurrence in the residual liver and hepatic arterial infusion chemotherapy (FAP) was performed. The recurrent lesion disappeared completely after 3 sessions of arterial infusion chemotherapy. The arterial infusion chemotherapy was continued in the outpatient clinic and the recurrent lesion is well controlled. At present, this patient has returned to social life, 2 years and 3 months after the hepatic resection. The utility of hepatic arterial infusion chemotherapy and hepatectomy for postoperative multiple hepatic metastasis from esophageal cancer was shown in the present case.     

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 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.     

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.     

A case of unresectable advanced gallbladder cancer treated by systemic chemotherapy combined with hepatic arterial infusion

A 53-year-old woman was revealed to have gallbladder cancer with liver metastases (H 1). Since a curative operation is impossible in this case, we started systemic chemotherapy employing S-1 combined with hepatic arterial infusion using epirubicin hydrochloride and mitomycin C. After three months, the primary lesion was reduced in size. The patient has been receiving systemic chemotherapy using S-1 only as an outpatient for 16 months. Although there is not enough evidence to support standard treatment, systemic chemotherapy combined with hepatic arterial infusion would improve the survival time without deterioration of quality of life in patients with advanced gallbladder cancer. This combined therapy should be considered one of the promising strategies for advanced gallbladder cancer.     

A case of advanced gastric cancer with hepatic metastasis successfully treated by combined chemotherapy with UFT and lentinan

We have experienced successful treatment of a hepatic metastasis of gastric cancer with UFT and lentinan. The patient was a 65-year-old male, who underwent distal gastrectomy for gastric cancer with hepatic and lymphatic metastases. After operation, administrations of UFT 300 mg/day and lentinan 2 mg/2 weeks were given, and the hepatic metastasis disappeared by 17 months. We performed a resection of the residual stomach and lymphatic metastasis at 52 months after operation. For over 5 years the patient has shown no evidence of a recurrence of the hepatic metastasis. This chemotherapy regimen was very effective and improved the patients quality of life.     

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.     

A case of large-cell lung cancer with liver metastasis successfully treated using combination chemotherapy with CDDP and vinorelbine

A 38-year-old woman presented to our hospital with the chief complaint of dyspnea. A chest radiograph showed pleural effusion of the right lung and a CT scan revealed liver metastasis. A tumor biopsy done under bronchoscopy revealed large-cell carcinoma of the lungs. She was given 4 courses of a combination therapy consisting of CDDP (80 mg/m2) and vinorelbine (25 mg/m2). The primary tumor in the right lung and liver metastasis were markedly reduced in size and a partial response was obtained. The combination therapy of CDDP and vinorelbine may become a standard chemotherapy for advanced non-small cell lung cancer.     

A case of postoperative hepatic metastasis from gastric cancer responding to hepatic arterial infusion chemotherapy of paclitaxel

A 70-year-old man underwent total gastrectomy for advanced gastric cancer in January 2000. He was treated with UFT of 300 mg/day after surgery. In December 2000, liver metastasis was detected. In January 2001, treatment was switched to oral administration of TS-1 at 100 mg/day. In April 2001, there were no extrahepatic lesions. However, the metastatic liver focus showed progression of the disease (PD). TS-1 was discontinued. In May 2001, a hepatic arterial injection reservoir was inserted. Thereafter, arterial injection chemotherapy with 5-FU was administered. However, in November, liver dysfunction was exacerbated, and computed tomography (CT) revealed PD. Therefore, in December, the above chemotherapy was switched to arterial injection of paclitaxel at 100 mg, which was administered once a week for 3 weeks and discontinued for the subsequent week. In March 2002, hepatopathy had subsided at the end of the 4th course, the performance status (PS) improved and CT revealed a minor response. In June 2002, the condition deteriorated to PD. However, there were no side effects other than alopecia. During the administration period, treatment at the outpatient clinic could be safely performed. These findings suggest that hepatic arterial injection therapy with paclitaxel for liver metastasis after surgery for gastric cancer is a useful second line for 5-FU-resistant patients.