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 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 sigmoid colon cancer with metastases of para-aortic lymph nodes treated with curative resection after irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy

A 54-year-old woman visited our hospital with a chief complaint of lower abdominal pain and melena. The patient was diagnosed with sigmoid colon cancer using colonoscopy. Abdominal CT revealed metastases to para-aortic lymph node, so our diagnosis was unresectable sigmoid colon cancer. She underwent a transverse colostomy to avoid stenosis. Two weeks after surgery, she underwent a 1-week chemotherapy regimen (CPT-11 80 mg/m(2)/week+5-FU 2,000 mg/m(2)/week+l-LV 250 mg/m(2)/week) modified AIO regimen combined irinotecan for 3 weeks, followed by a 1-week rest interval as one course. Throughout the period of treatment, there was no adverse event, and this regimen has been maintained for 5 courses. After 5 courses of chemotherapy, primary tumor and metastases to para-aortic lymph nodes were remarkably reduced on colonoscopy and abdominal CT. So, she could undergo curative resection. Pathological efficacy was Grade 3, a complete response. This combination therapy may well be useful for advanced colon cancer patients.     

A case of recurrent rectal cancer with lymphangiosis carcinomatosa successfully treated with modified FOLFOX6 therapy

A 56-year-old woman with multiple lung metastases and lymphangiosis carcinomatosa due to recurrent rectal cancer was treated with chemotherapy of modified FOLFOX6 (mFOLFOX6) regimen: l-leucovorin (l-LV 200 mg/m(2)) and oxaliplatin (L-OHP 85 mg/m(2)) were given as a 2-hour infusion followed by bolus injection of 5-FU 400 mg/m(2) and a 46- hour infusion 5-FU 2,400 mg/m(2) every two weeks. Since partial response was achieved and dyspnea was remarkably improved, she was discharged without oxygen therapy after 5 courses.     

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.     

Retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer

Ten cases of advanced and metastatic colorectal cancer treated with irinotecan plus fluorouracil and l-leucovorin systemic chemotherapy (CPT-11/5-FU/l-LV) were investigated. The 10 patients consisted of 7 males and 3 females with a mean age of 64.3 years. We diagnosed adenocarcinoma of the colon in 2 patients and of the rectum in 8 patients. Five patients had liver and lung metastases, 1 had lymph node metastases, 1 had bone marrow metastases and 3 had recurrence in a pelvic lesion. All patients underwent 3-week chemotherapy regimen (CPT-11 50 mg/m2/week + 5-FU 400 mg/m2/week + l-LV 20 mg/m2/week). Five patients received this regimen as a first-line chemotherapy and the other patients as a second-line chemotherapy after 5-FU/l-LV chemotherapy. The effect was CR or PR in all patients receiving the regimen as a first-line chemotherapy. The progression free survival time was 6.8 months and mean survival time was 10.0 months in the first-line patients. Otherwise, all second-line patients had PD. The suppression of white blood cells (grade 1 or 2) was seen in 4 patients. All patients were able to receive the systemic chemotherapy in the outpatient setting. CPT-11/5-FU/l-LV chemotherapy appears to be an effective first-line chemotherapy for advanced and metastatic colorectal cancer.     

A case report--combination chemotherapy with oral UFT and CPT-11, 5-FU, l-LV by hepatic arterial infusion for multiple hepatic metastasis from sigmoid colon cancer

A 64-year-old woman was diagnosed with multiple hepatic metastases from sigmoid colon cancer. She underwent resection of the colon and catheter insertion into the hepatic artery for arterial infusion in August 2006. She was then treated with postoperative combination chemotherapy consisting of UFT and CPT-11, 5-FU, l-LV. UFT was administered orally at 400 mg/body/day every day and CPT-11 was injected at 100 mg/body/week, 5-FU at 750 mg/body/week, and l-LV at 300 mg/body/week for 8 continuous weeks. After 2 months of the chemotherapy, the metastatic liver tumors disappeared. So hepatic arterial infusion with the same regimens was injected once every month 4 more times. Oral UFT was administered every day. After 6 months of the combined chemotherapy above, we judged the effects of the chemotherapy to be a complete response. Then the chemotherapy was followed by oral UFT only. As severe nausea and vomiting were seen in this patient with an initial dose of 150 mg/body/week of CPT-11 at first, we reduced the dose of CPT-11 to 100 mg/body/week. From then, outpatient care was possible because no severe events were observed. Combined chemotherapy consisting of oral UFT and CPT-11, 5-FU and l-LV by hepatic arterial infusion is suggested to be a new and effective treatment for multiple liver metastases from colorectal cancer.     

A case of colon cancer with multiple liver, lung and bone metastases successfully treated with combined weekly high-dose 5-FU (WHF) chemotherapy with UFT and CPT-11

A 54-year-old woman who had ascending colon cancer with multiple liver and lung metastases underwent rt. hemicolectomy and catheter insertion into the gastroduodenal artery for arterial infusion chemotherapy. On postoperative day 7, she had nausea and vomiting due to the enlarged multiple liver metastases on lateral segment. Intraarterial infusion of 5-FU 1,000 mg/m(2) for 5 hours weekly (WHF: weekly high-dose 5-FU) was started at first. After 3 courses, her symptoms improved, oral intake could be started, and liver metastases showed significant reduction on abdominal CT. Three months after surgery, bone scinti revealed multiple bone metastases. Combined HAI (5-FU: 600 mg/m(2)/3 hr) chemotherapy with UFT (400 mg/body) + CPT-11(80/body) and UFT (400 mg/body)/LV (75 mg/body) + CPT-11(100 mg/body) were effective for highly advanced colon cancer in terms of QOL. Eight months after surgery, she was doing well and the chemotherapy was continued. WHF therapy was effective for digestive symptoms due to liver metastasis.     

Four cases of advanced colorectal cancer successfully treated with irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy

We successfully treated four advanced colorectal cancers with irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. We diagnosed moderately-differentiated adenocarcinoma of the colon in two patients and of the rectum in two patients. We recognized lymph node metastases in one patient and liver metastases in three patients at the time of operation. After excision for a lesion of the colon or the rectum, all patients underwent a 2-week chemotherapy regimen (CPT-11 100 mg/m2/week + 5-FU 500 mg/m2/week + l-LV 10 mg/m2/week). The effect was PR in all patients. The progressive free survival time was 9.5 months and survival time ranged 5-18 months. Grade 3 diarrhea and leukopenia were seen in one patient. All other adverse reactions were mild (grade 1 or 2). CPT-11/5-FU/l-LV combination chemotherapy appears to be effective for advanced and metastatic colorectal cancer.     

A phase II study of irinotecan plus chronomodulated oxaliplatin, 5-fluorouracil and folinic acid in advanced colorectal cancer patients

The combination of irinotecan (CPT-11), oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and folinic acid (FA) is one of the possibilities to overcome chemoresistance in advanced colorectal cancer (ACRC) patients. The aim of this study was to determine the tolerability and activity of CPT-11 plus chronomodulated infusion of L-OHP, 5-FU and FA in ACRC patients. A total of 35 patients (91% pretreated, 77% with CPT-11, 54% with L-OHP, 42% with both) were treated every 3 weeks with CPT-11, 180 mg m(-2) day 1 i.v., plus L-OHP, 20 mg m(-2) day(-1), 5-FU, 700 mg m(-2) day(-1) and FA, 150 mg m(-2) day(-1), all three drugs from day 2 to day 5 by chronomodulated infusion. The patients' (pt) data were as follows: male/female 21/14; median age 58 years (range: 38-70); PS 0: 26 pts (74%), PS 1: 8 pts (23%), PS 2: 1 pt (3%); primary tumour colon/rectum 26/9; involved organs: 1, 14 pts (40%); 2, 17 pts (48%); >or=3: 4 pts (11%); previous chemotherapy lines 1: 12 pts (34%), 2: 10 pts (28%), >or=3: 10 pts (28%). A total of 221 courses (c) were performed; no grade 4 toxicity was observed with only one grade 3 (G3) neutropenia and thrombocytopenia (3%) in one out of 221 courses (<1%). Maximal toxicity (G3) was nausea and diarrhoea in 10 pts (28%), occurring in 14 out of 221 c (6%) and 12 out of 221 c (5%) respectively. Seven patients achieved a partial response (20%, confidence interval (c.i.) 6.8-33.3) and one patient a complete response (2.9%, c.i. 0-8.4), for a total overall response rate of 22.9% (c.i. 9-36.8); 15 out of 35 (42.9%, c.i. 26.5-59.3) had stable disease and 12 out of 35 (34.3%, c.i. 18.6-50) patients underwent a progression. In conclusion, this four-drug regimen is feasible in advanced pretreated ACRC patients with no significant haematological toxicity and acceptable diarrhoea. The activity of this combination is currently studied in EORTC 05011 study.     

Two cases of multiple liver metastases from colorectal cancer which responded well to hepatic arterial infusion (HAI) using 5-fluorouracil and l-leucovorin

We present two cases of multiple liver metastases from colorectal cancer, which did not respond to hepatic arterial infusion (HAI) using 5-fluorouracil (5-FU 1250 mg/body weekly) alone, but responded to HAI using 5-fluorouracil (5-FU 750 mg/body weekly) and l-leucovorin (l-LV 50 mg/body weekly) achieving a complete response (CR). The first case: A 71-year-old man with Stage II rectal cancer who underwent lower anterior resection developed multiple liver metastases 5 months after the surgery. As the weekly HAl using 5-FU for nine courses showed no response, l-LV was combined, and the liver metastases disappeared after 10 courses to achieve CR. The second case: A 65-year-old man with rectal cancer, sigmoid colon cancer and multiple liver metastases underwent lower anterior resection. The weekly HAl using 5-FU for seven courses showed no response. By combining 5-FU to l-LV, the liver metastases disappeared after fifteen courses. No toxic event was observed. In these two cases, it was suspected that a reduced foliate may be responsible for the failure by the 5-FU treatment alone.     

A case of recurrent colon cancer with urinary bladder, para-aortic lymph nodes, and spleen metastases successfully treated with CPT-11

The patient was a 71-year-old woman with sigmoid colon cancer with urinary bladder invasion, for which sigmoidectomy with D 3 lymphadenectomy and partial cystectomy was performed. After surgery, the patient was started on 4 courses of 6-week systemic chemotherapy (500 mg/m(2) 5-FU and 200 mg/m(2) l-LV weekly). However, 4 months later, CT revealed local recurrence in the urinary bladder and recurrence in the para-aortic lymph nodes and spleen. Therefore, low-dose CPT-11 therapy (40 mg/m(2) once per week) was instituted, which achieved a complete response as revealed by CT for response evaluation 5 months after the start of therapy. Up to the present, after 8 months no recrudescence or recurrent lesions in other organs have been observed. The patient developed mild side effects such as grade 1 nausea, anorexia, and leukopenia, but has a well-maintained QOL.     

A retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer

We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l-LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer.     

A case of advanced rectal cancer responding to neoadjuvant chemotherapy with CPT-11, 5-FU and l-LV after coronary artery bypass graft

A 75-year-old man was referred to our hospital with a diagnosis of lower rectal cancer. Unstable angina attack occurred after admission and cardiac angiography revealed stenosis of three coronary arteries which were treated by percutaneous transluminal coronary angioplasty unsuccessfully. Coronary artery bypass graft was performed after colostomy. It is possible for operative stress, extracorporeal circulation and blood transfusion to diminish immunocompetence and increase the risk of recurrence. Therefore, CPT-11/5-FU/l-LV combination therapy (CPT-11 80 mg/m(2), 5-FU 500 mg/m(2), l-LV 250 mg/m(2) day 1, 8, 15 every 5 weeks) was carried out as neoadjuvant chemotherapy. The tumor decreased in size, and the level of tumor marker was normalized after two courses of the combination therapy. The patient is alive without recurrence three years after abdominoperineal resection.     

Two cases of metastatic or recurrent rectal cancer responding to combined chemotherapy of low-dose CPT-11 and 5'-DFUR as second-line chemotherapy

We performed combined chemotherapy of low-dose CPT-11 and 5'-DFUR as second-line chemotherapy in 2 cases of non-resectable metastatic or recurrent rectal cancer. The first patient was a 61-year-old male who had rectal cancer with liver and lung metastases. The second patient was a 76-year-old male who had initial recurrent rectal cancer with multiple liver metastases. Both patients were given first-line chemotherapy of 5-FU + l-LV. CPT-11 was administered at 60 mg/body on day 1, 8 and 15 of a 4-week course by intravenous infusion as outpatient treatment. Furthermore, 5'-DFUR was administered orally at 800 mg/body every day. Consequently, we obtained a decrease in the tumor markers and a reduction of liver metastases in 2 patients after 3 months, Adverse reactions such as myelosuppression and diarrhea were not observed. This treatment could be continued in safety with good QOL on an outpatient basis. These cases suggest that this combined chemotherapy of low-dose CPT-11 and 5'-DFUR may be an effective treatment for non-resectable colorectal cancer in the future.     

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.     

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.     

CR of rectal cancer and synchronous liver and lung metastases obtained with TS-1 plus CPT-11 combination therapy--case report

The patient was a 44-year-old male in whom low anterior resection of the rectum, partial pneumonectomy, and liver biopsy were performed because of suspicion of synchronous liver and pulmonary metastases of rectal cancer which caused familial adenomatous polyposis. Because anticancer drug sensitivity testing by the HDRA method performed on tissue collected from the cancer immediately postoperatively revealed sensitivity to 5-FU and CPT-11, and measurement of nucleic acid metabolizing enzymes showed a high level of DPD, a 5-FU metabolizing enzyme, combination therapy with TS-1 and CPT-11 was started. TS-1, 120 mg/body, was administered on 14 consecutive days followed by a 7-day rest period, and CPT-11, 120 mg/body, was administered on day 1 and day 8. One cycle was defined as 3 weeks,and cycles were repeated. Grade 2 diarrhea occurred, but the CPT-11 dose was reduced to 100 mg/body, and treatment was continued. CR was achieved when the 4th course had been completed. Thoracic and abdominal CT was performed after 4 courses, but no recurrent foci were detected in the residual lung tissue, and all of the metastatic liver foci had resolved. To date 6 courses have been completed, and no relapses have been detected by thoracic CT. We report a case in which it was possible to predict efficacy as a result of treatment based on anticancer drug sensitivity testing and measurements of nucleic acid metabolizing enzymes.     

A case of remnant liver metastases after resection of liver metastases from rectal cancer following treatment with 5-FU, L-OHP and CPT-11, with markedly effective treatment by cetuximab plus S-1

FOLFOX or FOLFIRI are commonly used as first- or second-line chemotherapy for unresectable colorectal cancer or its metastases.Recently, it had become a trend to add bevacizumab or cetuximab(Cmab)limited to the K-ras wild-type or panitumumab(Pmab)limited to the K-ras wild-type.At the present time, a common third-line chemotherapy is CPT-11 plus Cmab limited to the K-ras wild-type, or Cmab/Pmab.However, the results are unsatisfactory.With Cmab plus S-1 we treated a case of remnant liver metastases from rectal cancer which was a K-ras wild-type, after treating 5-FU, L-OHP and CPT-11. The tumor marker dropped and 7 focuses of liver metastases disappeared after 6 courses of treatment(complete response: CR in)and CR was achieved after 9 courses treatment.After 10 courses of treatment, a new lesion appeared on S5 of the liver and we performed percutaneous radiofrequency ablation.     

A case of resected spinal metastasis following colectomy and hepatectomy for descending colon carcinoma

The patient was a 49-year-old man. In 1995, he underwent left hemicolectomy for descending colon carcinoma, and in 1996, partial hepatic resection was performed for liver metastasis. Post-operative chemotherapy was performed with 5'-DFUR. Five years later, he had lumbar and femoral pain. X-ray and MRI examination revealed a compression fracture and a spinal tumor at the XII thoracic vertebra. Though chemoradiotherapy was performed, the symptoms of pain, numbness and muscle weakness progressed. A resection of the metastatic spinal tumor was performed. Following several systemic chemotherapies, such as 5-FU/l-LV, CPT-11 + 5-FU/l-LV and low-dose CPT-11/UFT, radiotherapy was performed for the progressed bone tumor. At 2 years after surgery, he is still able to walk and no other site of recurrence has been detected.