Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM. From January 1988 until April 1994, 88 patients with recurrent or metastatic AGC were randomly received 5FU, EPI, MMC with (group A) or without (group B) LV. Between the two arms of the study no difference was noticed in sex, performance status, primary site of tumor, and lymph node metastases. Therapy included group A (5FU 600 mg/m2/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m2/day, i.v. bolus, on days 1 and 29, MMC 10 mg/m2/day, i.v. bolus, on day 1) and group B (the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there were two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significantly higher number of patients achieving stable disease was observed in group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). There were more patients with progressive disease in group A 25 (59%) than in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted in mean duration of response: group A, 15.8 (6-31) weeks; and group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients from disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not evaluable because they abandoned therapy after the first cycle. Toxicity was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically different when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate was increased in the schedule with the addition of LV, at the cost of increased toxicity and with no difference in survival. A randomized trial comparing FEM-LV with new generation regimens would determine whether the addition of LV qualifies FAM equally active with these.
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PMID:5-Fluorouracil, epirubicin, and mitomycin C versus 5-fluorouracil, epirubicin, mitomycin C, and leucovorin in advanced gastric carcinoma. A randomized trial. 882 83

The liver is one of the most frequent sites of metastatic growth, in particular from digestive malignancies (DM). The first goal is to reduce the incidence of metastases. Adjuvant systemic chemotherapies have been demonstrated to reduce the recurrence rate and to improve survival in Dukes C colon cancer. Fluorouracil is the pivot of adjuvant treatment modulated by Leucovorin or Levamisol. A short postoperative administration of fluorouracil by intraportal route has been tested, but the results are controversial. Adjuvant treatments for different DM are under investigation. When hepatic metastases are clinically evident, therapeutic decisions depend on several factors: site and nature of primary, extent of hepatic and extrahepatic disease, patient characteristics, efficacy of treatments. A staging system should be adopted to allow a rational approach. In selected cases a locoregional treatment can achieve consistent results. Hepatic Intrarterial Chemotherapy (HIAC) for colorectal metastases achieves objective responses in more than 50% of patients. Survival seems positively affected. When feasible, Ro hepatic resection is the most effective treatment, five-year survival rate being about 30% when metastases are from colorectal cancer. Since the liver is the most frequent site of recurrence after resection, repeat resection have been successfully performed.
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PMID:[Liver metastasis: therapeutic strategy]. 921 69

A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation.
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PMID:[An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas]. 1108 47

A 57-year-old female diagnosed with advanced gastric cancer with multiple organ metastases was treated by various intra-arterial chemotherapies. After surgical resection of the tumor, adjuvant chemotherapy was carried out. Continuously administered 5-fluorouracil of 250 mg/day made it possible to control the growth of the liver metastases. Extrahepatic metastases were kept under control by administering 30 mg of methotrexate, 750 mg of 5-fluorouracil and 30 mg of Leucovorin per/day/week, and 60 mg/day biweekly of cisplatinum via an abdominal artery infusion port. Owing to this multiple infusion route and chemotherapy regimen, the patient lived for 18 months after her first diagnosis of gastric cancer with multiple liver metastases. Although liver metastases may respond to hepatic arterial infusion chemotherapy, extrahepatic metastases lead to poor prognosis. Given the above results, intra-abdominal aorta chemotherapy may be effective for extrahepatic metastases since this method gives high concentration of the anticancer agents at tumor sites with a low incidence of side effects.
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PMID:[A case of advanced gastric cancer with multiple liver metastases partially responding to combination intra-arterial chemotherapy via the hepatic artery and abdominal aorta]. 1170 20

Colorectal Cancer (CRC) is the most frequent digestive cancer in France and a major public health problem. The benefits of adjuvant chemotherapy after curative resection of Stage III CRC has been clearly demonstrated. For metastatic CRC, palliative chemotherapy allows an improvement in survival duration and quality of life compared with symptomatic treatment. 5-FU/Leucovorin chemotherapy (Mayo Clinic protocol and LV5FU2) is the standard adjuvant therapy. The addition of irinotecan (FOLFIRI) or oxyplatin (FOLFOX) to this regimen may improve response in palliative situations. These two regimens have shown their superiority to 5FU/Leucovorin in both tumor response and survival. A good objective response to palliative chemotherapy may allow for a secondary resection of hepatic metastases as part of a multidisciplinary approach. Current studies aim to define: 1) optimal treatment strategies (which drug protocols? in what order?) as they apply to tumor spread, drug toxicity profiles, the general state of the patient, and the desired therapeutic effect; 2) evaluation of new drugs and novel therapeutic approaches. Despite notable progress, the prognosis still remains grim with a survival of only 40% at 5 years. Any improvement in results will require not only an improvement in chemotherapy but also an improvement in methods of early diagnosis (systematic mass screening) which would permit the diagnosis of CRC at earlier stages where curative resection is feasible.
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PMID:[Chemotherapy for colorectal cancers]. 1270 55

A 61-year-old man underwent curative low anterior resection for rectosigmoid colon cancer. Follow-up ultrasonography revealed unresectable multiple liver metastases at 10 months after surgery. Arterial infusion therapy with 5-fluorouracil (5-FU) was given at 1,500 mg every 2 weeks up to a total dose of 37.5 g, resulting in complete remission (CR) of the liver metastases. However, recurrence was seen 4 months after CR. Following partial hepatectomy and local ablation therapy, he received multidisciplinary treatment including local ablation therapy, arterial infusion of 5-FU and mitomycin C, and systemic chemotherapy with 5-FU/Leucovorin/CPT-11. The patient died of liver failure at 3 years and 7 months after the detection of hepatic metastases. If arterial infusion therapy achieves CR of unresectable hepatic metastases from colorectal cancer, the patient may survive for several years with multidisciplinary treatment including surgery, local ablation therapy, and systemic chemotherapy.
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PMID:[A case of unresectable liver metastases from rectosigmoid colon cancer with survival for over 3 years after multidisciplinary treatment]. 1461 6

We report a patient with multiple hepatic metastases from colorectal cancer effectively treated by hepatic arterial infusion therapy (5-FU/LV therapy). The patient was a 55-year-old man with sigmoid colon cancer and multiple hepatic metastases, 5 cm in diameter, in both lobes of the liver. First, we locally controlled the sigmoid colon cancer by sigmoid colectomy (with D3 lymph node dissection). After resection of the primary cancer lesions and dissection of the lymph nodes, we treated the patient by systemically administering 4 courses of Leucovorin/5-FU (once weekly for 6 weeks per course) from a port-catheter system during hospital stay and in the outpatient clinic after hospital discharge. Assessment of therapeutic effects by CT showed CR in the patient. CEA levels, which were abnormal before and after surgery, decreased to normal at the end of chemotherapy. After 1 year, neither CT evidence of tumor enlargement in the liver nor re-increase in CEA levels has been noted. Although the patient experienced side effects such as pigmentation, grade 1 loss of appetite, and leukopenia, he was able to maintain his QOL in the absence of severe side effects.
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PMID:[A case of multiple hepatic metastases from colorectal cancer effectively treated by arterial infusion therapy with Leucovorin/5-FU]. 1465 Sep 73

We performed radio-frequency ablation (RFA) therapy combined with intra-arterial chemotherapy for a 71-year old female gastric cancer patient with liver metastasis. She underwent total gastrectomy due to advanced gastric cancer in July of 1996. Because CT scans revealed multiple liver tumors with her, she also underwent intra-arterial chemotherapy comprising of 5-fluorouracil, cis-platinum and Leucovorin. Although her liver tumors decreased in size and number, after 9 months, we had to remove the catheter because of hepatic artery obstruction. Immediately after the removal, 5 hepatic metastases appeared, which were 3.5 cm in maximum diameter. After RFA therapy, CT scans revealed homogenously attenuated lesions. Liver biopsy demonstrated a complete coagulation necrosis. She is currently alive going into 19 months after liver metastasis and 7 months after RFA.
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PMID:[A case of gastric cancer patient with liver metastasis treated by radiofrequency ablation therapy combined with intra-arterial chemotherapy]. 1555 99

The liver is the most frequent metastatic site from colorectal cancer, and the control of liver metastasis is an important issue in the treatment of progressive colorectal cancer. Hepatic arterial infusion (HAI) therapy can achieve a high drug concentration in the liver and relatively low level in the systemic circulation because of the first pass effect of the drug metabolism. With the high response rate, several reports have failed to show a significant survival benefit of HAI monotherapy, partially due to its inability to control extrahepatic metastasis. In this report, we used oral tegafur/uracil (UFT) and Leucovorin (LV) combined with HAI of 5-FU for four patients with liver metastasis of colorectal carcinoma. One of two patients with unresectable multiple hepatic metastases could undergo resectional surgery after 5 courses of this therapy. Two other cases in an adjuvant setting have been surviving free of tumors. In this series, adverse effects of this therapy were acceptable, including one case of grade 3 thrombocytopenia. The benefit of this combined therapy for survival in a case of liver metastasis from CRC remains to be evaluated. We are planning phase I and II clinical studies to evaluate the efficiency and feasibility of this combination therapy.
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PMID:[Combined chemotherapy with oral leucovorin (LV) + tegafur/uracil (UFT) and hepatic arterial infusion (HAI) therapy for liver metastasis of colorectal cancer]. 1604 71

We describe our experience with a patient who had undifferentiated gastric carcinoma with extensive lymph node metastasis, including para-aortic lymph-node metastasis, and had a complete response to induction therapy with methotrexate plus 5-fluorouracil (sequential therapy with MTX, 5-FU, and Leucovorin) and secondary treatment with oral TS-1. The patient was a 71-year-old woman with a massive gastric tumor (signet ring cell carcinoma), occupying most of the stomach. A computed tomographic (CT) scan revealed para-aortic, celiac, and common hepatic lymph-node metastases. Stage IV disease was diagnosed. Palliative total gastrectomy was performed to control bleeding and to improve oral intake of food. Two courses of induction therapy with MTX, 5-FU, and Leucovorin were started 3 weeks after surgery. A CT scan revealed residual lymph node metastasis. The response was assessed to be no change, but the levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 improved from 7,028 ng/ml and 726 U/ml 3 weeks after surgery to 2,832 ng/ml and 281 U/ml, respectively. Secondary treatment with oral TS-1 was begun, and a CT scan showed distinct shrinkage of lymph-node metastases. There was no serious toxicity. The levels of CEA and CA19-9 decreased markedly to 2.9 ng/ml and 16 U/ml, respectively, about 6 months after surgery and remained at 3.7 ng/ml and 16 U/ml, respectively, about 1 year after surgery.
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PMID:[Stage IV gastric cancer patient who underwent palliative gastrectomy showing complete response to induction therapy with methotrexate plus 5-fluorouracil and secondary treatment with oral TS-1]. 1612 21


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