Successful treatment of liver metastasis and extrahepatic metastasis with hepatic arterial infusion of CDDP, CPT-11, and 5-FU

A 63-year-old man, who had been operated with right hemicolectomy 1 year and 3 months ago, had giant liver metastasis, lung metastasis, and local dissemination tumor due to ascending colon cancer. He was treated by systemic chemotherapy with 5-FU and the treatment evaluation was PD on CT. After admission to our hospital, he was treated by hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU. After 3 courses of the treatment, each recurrent lesion decreased on CT and the CEA level decreased. There were no side effects except mild diarrhea. We believe hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU may be an effective strategy against liver metastasis and extrahepatic metastsis due to colon cancer.     

A case of colon cancer with liver and lung metastases-efficacy of CPT-11/5-FU/l-LV (IFL) as part of ambulatory treatment

In July 2003, a 59-year-old man underwent a right hemicolectomy for sigmoid colon cancer. Hepatic intraarterial injection therapy with 5-FU/CDDP was not only ineffective against a liver metastasis but a lung metastasis was also found, and therefore systemic chemotherapy with CPT-11/5-FU/l-LV (IFL) was administered. After onetime IFL therapy, the CPT-11 was withheld due to ileus. Although 5-FU/l-LV therapy was administered, it was ineffective. IFL therapy was again performed, with the dose decreased by 20%, as part of ambulatory treatment. Not only the liver metastasis but also the lung metastasis decreased significantly in size after one course. In addition, no severe adverse reactions were observed during the treatment, which enabled the therapy to be continued as part of an ambulatory regimen. The results suggest that IFL therapy is effective against colon cancer with lung/liver metastasis and can be administered as part of ambulatory treatment.     

A case report of colon cancer with liver and lung metastases responding to combination chemotherapy with l-LV, 5-fluorouracil and CPT-11

A 58-year-old man who had colon cancer with liver and multiple lung metastases underwent ileocecal resection on May 10, 2002. MTT assay of 5-FU and CPT-11 was performed with resected material, with both medicines accepted for sensitivity. On June 4, he received combination chemotherapy with CPT-11 + 5-FU/l-LV. The liver metastasis disappeared and was judged CR from a CT of the abdomen. Almost all the multiple lung metastases had disappeared or were decreased in size. They were therefore judged NC from a CT of the chest. Moreover, CEA and CA19-9 decreased to within normal limits. While he was receiving bimonthly chemotherapy with only CPT-11 as a maintenance therapy, liver and lung metastases did not change. Combination chemotherapy with CPT-11 + 5-FU/l-LV is effective. The anticancer drug sensitivity examination is only one index, however. Considering adverse effects and medical costs, individualized therapy based on the sensitivity test for anticancer drugs should be performed.     

A case of gastric cancer with multiple liver metastasis responding to combination therapy of CPT-11 and CDDP

A 63-year-old man suffering from advanced gastric carcinoma after distal gastric resection had multiple liver metastases 5 months after the operation. He underwent 3 courses of combination chemotherapy of 5-FU 600 mg/day with CDDP 50 mg/day, etoposide 100 mg/day and Leucovorin 30 mg/day for 5 days (FLEP), but progressive disease (PD) was noted. One additional course of combination chemotherapy with CPT-11 140 mg/day and CDDP 40 mg/day biweekly was performed and a complete response (CR) was noted. After 4 months, recurrence of a liver metastasis on S8 was demonstrated and 2 courses of the same chemotherapeutic regimen were carried out. Over 5 months, recurrence of the liver metastasis showed no change (NC) and resection of S8 of the liver was performed. No recurrence was after 6 months, but the patient died 34 months after the first detection of the occurrence of multiple liver metastases. The combination chemotherapy of CPT-11 with CDDP was also administered to other patients at our outpatient clinic and seems to be useful therapy for improving outcome.     

Second-line chemotherapy with bi-weekly CPT-11 and cisplatin for recurrent colorectal cancer resistant to 5-FU based chemotherapy

Second-line chemotherapy with bi-weekly CPT-11 and cisplatin (CDDP) was given to 19 patients with recurrent colorectal cancer resistant to 5-FU based chemotherapy. The 19 patients consisted of 18 men and 1 woman with a mean age of 61.3 years. Nine patients had liver metastasis, 4 had lung metastasis, 2 had local recurrence, 2 had both local recurrence and lung metastasis, respectively, 1 had local metastasis and lymph node metastasis, and 1 had bone metastasis. CPT-11 (80 mg/m2) and CDDP (30 mg/m2) were administered bi-weekly. The objective overall response rate was 15.8%. The time to progression was 146 days, and the median survival time was 477 days. Grade 3 leucopenia and nausea occurred in 1 patient (5.3%). CPT-11 and CDDP treatment should be considered as second-line chemotherapy for colorectal cancer resistant to 5-FU based chemotherapy.     

A case of advanced gastric cancer with liver metastasis completely responding to CPT-11+low-dose 5-FU+CDDP chemotherapy

The case was a 54-year-old man with type-3 gastric cancer in the cardia accompanied by multiple liver metastasis. He received combination chemotherapy consisting of CPT-11 (60 mg/body, day 1 and 8)+low-dose 5-FU and CDDP (5-FU 500 mg/body/day and CDDP 5 mg/body/day, day 1-5 and 8-12, continuous infusion) every 3 weeks. The initial 2 courses were administered on an inpatient basis,and further courses as an outpatient. After 7 courses of therapy without severe adverse events, not only primary lesion but also hepatic metastasis disappeared. He has been free from disease for 4 months, and chemotherapy was further continued with TS-1 (100 mg/body, day 1-14)+CPT-11 60 mg/body, day 1, 8), every 3 weeks. CPT-11 in combination with low-dose 5-FU+CDDP can be one of the most effective regimens for unresectable advanced gastric cancer.     

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.     

Long survival of a colon cancer case with multiple liver metastases cured by multidisciplinary therapy

The patient was a 79-year-old a man who had a sigmoid colon resection for sigmoid colon carcinoma in another hospital 11 years ago. Four years later,he was noted to have multiple unresectable hepatic metastases on CT. Therefore,intrahepatic arterial and portal infusion with CDDP 10 mg + 5-FU 250 mg, respectively,were started. His CEA level decreased to the normal range,and a partial response (PR) was achieved. But two years later, the CEA level increased again,so radiofrequency ablation (RFA) therapy was given during abdominal surgery. Then, IFL, CPT-11+S-1, and FOLFOX were administered. Currently, the patient is being treated as an outpatient with CPT-11+S-1. The patient's multiple hepatic metastases were treated with multidisciplinary therapy, and the man has lived for 6 years 11 months since his first hepatic metastases were noted. The multidisciplinary therapy that was used lengthened this patient's life.     

A case of peritoneal dissemination of gastric cancer successfully treated by irinotecan combined with cisplatin

We report a case of a 59-year-old man with advanced gastric cancer. Distal gastrectomy with lymph node dissection (D1) was performed. Pathological staging was IV (T3N1CY1), and the operation resulted in curability C. The serum CA19-9 level before the operation was 201 U/ml, and it did not normalize 3 months after the operation. Postoperative chemotherapy (TS-1, 100 mg/day) was performed. Because the tumor markers such as CEA and CA19-9 level elevated 5 months after the operation, triweekly docetaxel therapy and TS-1 administration (days 1-14) were performed. We disbontinued this therapy after 2 courses due to adverse reactions, such as leukopenia (grade 4) and liver dysfunction (grade 2). Peritoneal dissemination was diagnosed by the appearance of ascites and thickness of the peritoneum 11 months after the operation. So the patient was treated with a biweekly combination chemotherapy of irinotecan (CPT-11 60 mg/m2) and cisplatin (CDDP 30 mg/m2). Eight courses of this therapy induced partial remission and normalization of the serum CEA level. No major adverse reaction to this therapy was observed. The partial remission and good patient's QOL were achieved during follow-up 7 months after the administration of CPT-11 plus CDDP. This case suggests that patients with recurrent peritoneal dissemination of gastric cancer could benefit from CPT-11 with CDDP combination therapy as a second-line or third-line treatment.     

Evaluation of combination chemotherapy with 5-FU, CDDP and CPT-11 for human gastric carcinoma transplanted into nude mice - comparative study of in vivo chemosensitivity test

We performed in vivo chemosensitivity tests on human gastric carcinoma. To evaluate the efficacy of some combined chemotherapy for human gastric carcinoma maintained in the subcutaneous space in nude mice, we designed the following six experimental groups: 1) 5-FU group, 2) CDDP group, 3) CPT-11 group, 4) combined therapy group of 5-FU and CDDP, 5) combined therapy group of 5-FU and CPT-11, and 6) combined therapy group of CPT-11 and CDDP. An in vivo nude mice assay was performed. Histopathological changes of the tumors in nude mice, treated with anti-cancer agents,were also evaluated and compared to the results of the nude mice assay.Based on histopathological grading,the true positive rate of the nude mice assay was 0%, the true negative rate was 83.3%, and the accuracy rate was 83.3%. CPT-11 appeared to be highly efficacious when given in combination with CDDP in human gastric cancer cell lines. These results suggest that combination chemotherapy with CPT-11 and CDDP is clinically effective for gastric cancer patients.     

A case of hepatic metastasis from colon cancer successfully treated with 5-FU, levofolinate (l-LV) and low-dose CPT-11

The patient was a 67-year-old man in whom hepatic metastasis from transverse colon cancer was detected 15 months after transverse colectomy (D2). We treated the patient by systemically administering 2 courses of 5-FU 750 mg/day with l-LV 350 mg/day (once weekly for 6 weeks per course). Assessment of therapeutic effects by CT showed PD in the patient. As a second-line therapy, we treated the patient by systemically administering 3 courses of 5-FU 750 mg/day, l-LV 350 mg/day and CPT-11 40 mg/day x 3 days (once a week for 4 weeks per course). After 3 courses of this chemotherapy, CT examination revealed a reduction in the tumor size of the liver, and CEA levels decreased at the end of this chemotherapy. This chemotherapy also showed no high-grade toxicities. l-LV/5-FU/low-dose CPT-11 seems to be effective for metastatic colon cancer, and safe from the toxicity standpoint.     

A case of AFP producing early gastric cancer successfully treated with small dose CDDP and 5-FU (PF) therapy]

A case of AFP producing early gastric cancer successfully treated with a small dose of CDDP and 5-FU therapy administered intermittedly is reported with a review of the literature. A 63-year-old male was admitted to our hospital because of liver metastasis with a high level of serum AFP (185.8 ng/ml) three months after gastrectomy. Systemic chemotherapy was performed twice with a regimen of CDDP 20 mg and 5-FU 750 mg/day in 5 days. After hepatic arterial infusion chemotherapy (HAIC) was performed once, the patient obtained partial response according to CT scan and was discharged. After he underwent HAIC once as an outpatient, liver metastasis completely disappeared 5 months after surgery. He was administered oral 5-FU, 150 mg and Krestin 3.0 g/day and underwent HAIC with CDDP 20 mg and 5-FU 750 mg/day every 2 weeks. After serum AFP level was returned to the normal range 7 months after surgery; HAIC was performed every 4 weeks and continued until one year after surgery. One year and 11 months after surgery, serum AFP remains within the normal limit and there is no evidence of recurrence.     

A case of long-term survivor with multiple pulmonary metastases of HCC after hepatic resection

A 52-year-old male was admitted to our hospital with huge hepatoma of the right lobe. He underwent a right lobectomy of the liver in July 1999. After five months from the surgery, multiple recurrences in the liver and lung were revealed with Computed tomography (CT). TAE was performed for intrahepatic recurrence and a combination therapy, consisting of UFT and interferon-alpha, was started for pulmonary metastasis. Then 5-FU/CDDP/interferon-alpha therapy was given in 2001 and TS-1/interferon-beta therapy was given thereafter in 2002. Consequently, the patient survived for 31 months with no disturbance in quality of life. No intrahepatic recurrence was also detected during the survival period. It was suggested that a good prognosis may be expected, even in the HCC case with distant metastasis after hepatic resection, if the primary cite was curatively treated.     

A long-term surviving patient with unresectable lung metastasis from colon cancer treated with intravenous administration of activated autologous lymphocytes and low-dose chemotherapy--a case report

We herein report a case of long-term surviving patient who was treated with intravenous administration of activated autologous lymphocytes and low-dose chemotherapy. The patient was an 82-year-old female. She underwent radical resection for sigmoid colon cancer in 1998 and right lobectomy of the liver for metastatic liver tumor in 2001. A follow up CT revealed the metastasis to the bilateral lung on November 2003. Then she received a treatment with UFT plus low-dose CPT-11/CDDP and activated autologous lymphocytes. Although the response of the treatment was SD, the serum CEA level decreased to a normal range. The treatment continued with delayed administration for 30 months while CEA and the size of the tumors increased very slowly. After that, her treatment was changed with a single administration of S-1. She obtained a 3.5 year survival with an inhibition of fast tumor growth by chemo-immunotherapy.     

A case of metastatic colon carcinoma in which a continuous intrahepatic artery-infusion of 5-FU leucovorin and cisplatin, and systemic chemotherapy with CPT-11 was very effective

We report a patient with metastatic colon carcinoma who was treated effectively with a continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and systemic chemotherapy with CPT-11. A 50-year-old man was diagnosed as having well differentiated adenocarcinoma of the sigmoid colon with multiple liver metastases in March, 1997. Left hemicolectomy and subsequent catheterization into the common hepatic artery via the gastroduodenal artery were performed in April, 1997. He was treated with 3 courses of continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and two courses of systemic chemotherapy with CPT-11 during hospitalization, followed by 6 courses of a similar intraarterial therapy in an outpatient setting. Reinstallation of the catheter into the hepatic artery via the femoral artery was performed because of occlusion of the reservoir. During the 6th course of intraarterial therapy, diarrhea, nausea, and vomiting appeared and angiography revealed a narrowing of the hepatic artery. Therefore, the intrahepatic artery-infusion therapy was reinitiated with doses of 5-FU, Leucovorin and cisplatin reduced to approximately 80%. After 5 courses of this therapy, the computed tomography scan showed a marked decrease in the size of the metastatic hepatic lesions by 90%, and the serum level of CEA decreased from 657.7 ng/ml to 4.5 ng/ml. No severe side effects were seen during the treatment. Though multiple lung metastases were indicated during the intrahepatic artery-infusion therapy, both the liver and lung metastases have been well controlled with continuous intrahepatic artery-infusion chemotherapy and systemic chemotherapy. The continuous intrahepatic arterial infusion of 5-FU, leucovorin and cisplatin appears to be very effective for the treatment of colon carcinoma with liver metastasis without reducing the quality of life.     

A case of gastric carcinoma with multiple skin, bone, and bilateral ovary metastasis; effective treatment by chemotherapy

A 40-year-old female visited our hospital with general malaise. She was diagnosed with gastric carcinoma with multiple skin, bone, and bilateral ovary metastases. Chemotherapy with 5-FU (1,000 mg/w) and cisplatin (10 mg/w) was performed in the outpatient clinic. Two years after the initial diagnosis, CEA was elevated. She then was given chemotherapy of CPT-11 (40 mg/w) in the outpatient clinic after 1 cycle of combined chemotherapy of CPT-11 and cisplatin. She died 38 months after the initial diagnosis. Weekly 5-FU/CDDP or low-dose CPT-11 appear to be effective for such a gastric carcinoma with systemic metastases without impairing quality of life.     

Low-dose CPT-11 against a recurrent rectal cancer--a case report]

We attempted a new regimen of low-dose CPT-11 on a 5-FU resistant recurrent rectal cancer patient with multiple lung metastases and a paraaortic lymph node metastasis. CPT-11 was administered at 25 mg/m2/day x 3/week by intravenous infusion. Serum CEA level decreased gradually with a half time of approximately 4 weeks. The lung metastases almost disappeared and the paraaortic lymph node was also reduced more than 50%. There were no adverse effects except slight alopetia. This treatment could be continued on an outpatient basis. These results suggest that low-dose CPT-11 may be more effective and tolerable than the conventional, CPT-11 therapy.     

Three cases with liver metastasis from gastric or colon cancer successfully treated with S-1 combined with CPT- 11

We report three cases with liver metastasis from gastric or colon cancer successfully treated with S-1 with CPT-11. Case 1: A total gastrectomy was performed for a gastric cancer located in the lower to upper body of the stomach(T3 (SE), N2, H0, P0, por 2, stage III B). Abdominal computed-tomography(CT)revealed a solitary liver metastasis in the S8 subsegment of the liver. We treated the patient with S-1 combined with CPT-11. Abdominal CT revealed a complete response(CR)after 5 courses. Case 2: Sigmoidectomy and partial resection of small intestine and abdominal wall were performed for sigmoid colon cancer. The intraoperative findings revealed liver metastases in left lobe of the liver(Si, N1, H1, P0, M0, tub 1, stage IV). After surgery, the patient was treated with S-1 combined with CPT-11. Abdominal CT demonstrated CR after 5 courses. Case 3: Laparoscopic right hemicolectomy was performed for ascending colon cancer( SE, N1, H0, P0, M0, tub 1, stage III a). Abdominal CT showed a solitary liver metastasis in the S6 subsegment of the liver 3 months after surgery. We treated the patient with S-1 combined with CPT-11. Abdominal CT revealed CR after 3 courses. The three cases are alive without any signs of recurrence.     

A case of colon cancer with liver metastases and lymph node metastases successfully treated with surgery followed by CPT-11 and 5-FU chemotherapy

A sixty-year-old woman underwent right hemicolectomy and D2 lymph node dissection. However, a solitary liver metastasis and para-aortic lymph node metastasis were detected three months after surgery. Chemotherapy using CPT-11 and 5-FU (civ) was immediately performed. After one course of this regimen, the chemotherapeutic effect was evaluated as a partial response (PR) in the liver metastasis, and as a complete response (CR) in the para-aortic lymph node. There was a massive therapeutic effect without side effects. Two further courses of chemotherapy were performed after changing from 5-FU to 5'-DFUR. Both regions of metastasis (liver and lymph nodes) continue to exhibit CR and the patient is free from any symptoms almost one year after surgery. The authors believe that this regimen is very effective and will contribute quality of life in advanced colon cancer patients.     

A case of liver metastasis from gallbladder cancer with marked response to arterial infusion chemotherapy

The patient was a 68-year-old woman who visited a nearby clinic with a chief complaint of right hypochondrial pain. A mass lesion in the gallbladder was found by ultrasonography. She was referred to our hospital for further examination and was diagnosed with gallbladder cancer. Cholecystectomy and bile duct resection were performed. Six months after the surgery, multiple liver metastases were found. A subcutaneous implant reservoir was placed in the hepatic artery from the right femoral artery. After arterial infusion chemotherapy by 5-FU and CDDP, or 5-FU alone, liver metastasis markedly responded and became undetectable, and therapy was therefore discontinued. The patient has been disease-free without any sign of recurrence for 7 months after CR was achieved. It is suggested that arterial infusion chemotherapy is useful and safe for the treatment of liver metastasis from gallbladder cancer.