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

The totally implantable infusion pump (Infusaid pump) for treating metastatic disease to the liver is a new treatment that is gaining widespread acceptance. However, as might be expected for any new major surgical procedure, there are increasing reports of complications. We report a complication in which duodenal atony was caused by the infusion of the chemotherapeutic agent (FUDR) into the stomach and duodenum. The atony was totally reversed by the subcutaneous administration of urecholine.
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PMID:A complication of the Infusaid pump: duodenal atony reversed by urecholine. 296 Aug 55

Locoregional, intra-arterial chemotherapy of liver metastases secondary to colo-rectal cancers is the least damaging among non-surgical treatments. In our experience of 58 cases treated during three years either with intermittent perfusions of 5 FU, or with continuous perfusion of FUDR (by pump), we observed 52% and 53% of objective responses with a survival rate at one year, of 73% and 90% respectively. However, this technique is limited because of locoregional complications and less effective, due to the development of extra-hepatic metastases. The proof of its effectiveness, in terms of survival, is currently being studied in the scope of a prospective and randomized trial with control group.
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PMID:[Locoregional chemotherapy of hepatic metastases of colorectal cancer]. 296 34

Cytotoxic chemotherapy was performed in a total of 18 patients (12 men, 6 women): 5 patients with colonic carcinoma and 1 patient with unknown primary lesion received 5 x 1000 mg 5-Fluorouracil (5-FU) at 4 week interval. The 5 following patients primarily suffering from colonic carcinoma were treated with 0.5 mg/kg BW FUDR continuously at 2 week interval. 5 further patients with colonic carcinoma sequential received Mitomycin C (8 mg/m2) and 4 x 1000 mg 5-FU. 2 patients with breast cancer were treated with 500 mg/m2 Cyclophosphamide, the same amount of 5-FU and 40 mg/m2 Methotrexate every 4 weeks. Chemotherapy was well tolerated by all patients. A clinically significant response, however, was seen in only 2 patients with breast cancer. In 8 patients a liver transplantat was performed, which was followed in 3 cases by ultra-high dose Cyclosphosphamide, lethal total body irradiation and autologous bone marrow transplantation. 1 further patient received polychemotherapy. At the time of this analysis only 3 patients were still alive at 61, 30 and 26 months with only 1 perioperative death. All 3 had meanwhile developed recurrent or metastatic disease. Because of these sobering results, liver transplantation for the treatment of non-resectable liver metastases has been abandoned, and regional chemotherapy is now only applied in patients with liver metastases from breast cancer and after resection of metastases in an adjuvant setting.
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PMID:[Our therapy concept in nonresectable liver metastases]. 297 81

Cure of primary liver tumours remains possible only by surgery and early diagnosis will therefore continue to be important; the value of regular screening of cirrhotic patients for development of HCC by ultrasound scanning and estimation of AFP is now established. Prognosis of irresectable HCC depends largely on the general condition of the patient at the time of diagnosis and is better in the absence of cirrhosis. Radiotherapy has little role in the management of patients with HCC, but benefit with acceptable morbidity may be obtained from parenteral chemotherapy, with doxorubicin or its derivatives used as single agents, or with a combination of 5-FU and methyl-CCNU. There may be advantage from regional therapy given via the hepatic artery and early results from the combination of embolization with arterial doxorubicin are encouraging. The use of radiolabelled antibodies to tumour-related determinants of hormonal manipulation show promise. Worthwhile results from the non-surgical management of peripheral (intrahepatic) cholangiocarcinoma and primary hepatic sarcoma remain scarce. Isolated hepatic metastases from colorectal primaries may be resectable; for those that are not, results from regional chemotherapy with 5-FU or FUDR are encouraging, but cost and high morbidity currently limit more general application.
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PMID:Chemotherapy and radiotherapy of malignant hepatic tumours. 303 57

Treatment of patients with hepatic metastases from colorectal cancer using hepatic artery floxuridine (FUDR) has been reported to induce high partial remission rates and perhaps prolonged survival. However, several investigators, including our own group, have obtained response rates of only 30%. Alkylating agents can increase the efficacy of antimetabolites. Based on clinical data and pharmacokinetic considerations the authors have combined FUDR with mitomycin C and carmustine (BCNU) by the arterial route. Thirty-six patients with hepatic metastases from colorectal cancer received FUDR 0.3 mg/kg/day 2 weeks of 4, mitomycin C 15 mg/M2 over 1 hour every 8 weeks, and BCNU 150 mg/M2 over 1 hour every 8 weeks--all via the hepatic artery using Infusaid pumps (Infusaid, Sharon, MA). The mitomycin C and BCNU were alternated monthly at the start of each FUDR cycle. The patient characteristics were as follows: 78% hepatomegaly, 44% also extrahepatic tumor, 42% prior systemic 5-fluorouracil. Combined partial and complete response rates were independent of prior chemotherapy: 71% if untreated, 67% with prior 5-fluorouracil. Median survival for the combined response/stable disease group was 13.7 months from the start of hepatic artery chemotherapy, and 4.5 months for the six nonresponders. Based on these data the authors have begun a randomized trial comparing single-agent FUDR to the FUDR, mitomycin C, BCNU combination.
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PMID:Treatment of metastatic colorectal cancer with hepatic artery combination chemotherapy. 308 Feb 21

Sixty-two patients with metastatic colorectal carcinoma involving the liver were treated by hepatic intra-arterial chemotherapy using an implantable infusion pump. The 53 patients with metastases confined to the liver had a median survival (MS) of 17 months and an objective response rate of 32%. Four patients (8%) demonstrated a complete response (CR), with normal abdominal computed tomography (CT) scan results and plasma carcinoembryonic antigen (CEA) levels, and 13 patients (25%) demonstrated a partial response (PR), with at least a 50% decrease in the liver lesions by CT scan and at least a 50% decrease in CEA levels. Thirty patients (57%) had stable disease (S), and six patients (11%) had no response (NR). Nine patients with extrahepatic tumor plus hepatic metastases had an MS of only 4.9 months. None of these patients had an objective response, and only four patients had S. Quality of response was clearly associated with longevity. Forty patients treated with floxuridine (FUDR) and mitomycin (M) (F + M) showed a 20% objective response rate, while the 13 patients treated with FUDR and dichloromethotrexate (DCMTX) (F + D) attained a 69% objective response rate. Although F + D treatment appears to be superior, there may have been selection biases that make such an observation only preliminary. Twenty-six (49%) of the 53 patients developed hepatitis during infusion chemotherapy, which resolved after temporary cessation of the chemotherapy. Of the 17 patients with CR or PR, 12 patients (71%) had hepatitis, whereas only 14 (39%) of the 36 patients with S or NR had hepatitis. Eleven patients had evidence of peptic ulceration by endoscopic examination during the infusion chemotherapy. All the ulcers healed after chemotherapy was discontinued.
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PMID:Therapy for metastatic colorectal cancer with hepatic artery infusion chemotherapy using a subcutaneous implanted pump. 315 93

Intraarterial regional chemotherapy for non-resectable, isolated colorectal metastases to the liver was performed in 121 patients via implantable pumps or infuse-a-ports. FUDR alone or in combination with 5-FU and Mitomycin C was administered in different modalities. Partial response rate ranged between 35 and 71%. Median survival since starting chemotherapy was so far 8-16 months. Extrahepatic relapse occurred in 45%, technical complications in 23% (pump) and 46% (infuse a port). Local toxic side effects strongly depended on drug dosage and application modus. These results corresponded with those of 647 German collective cases and 490 cases from American literature.
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PMID:[Locoregional chemotherapy of liver metastases of colorectal cancer]. 343 Dec 61

Thirty-two patients with hepatic metastases colorectal carcinoma were treated with hepatic artery infusion (HAI) employing 5-fluorouracil (5-FU) and mitomycin-C (mito-C). Catheters were placed percutaneously via the femoral artery. Two schedules were employed: (I) 5-FU 1,200 mg/m2 IA (D1-4) and mito-C 8 mg/m2 IA (D1 + D4); (2) 5-FU 1,200 mg/m2 IA (D1-6) and mito-C 8 mg/m2 IA (D1 + D4). Courses were repeated every 4 weeks. Thirty patients with measurable disease were evaluable, 22 received schedule I and 8 patients schedule II. Complete response occurred in two patients (6.7%) and partial response in 13 patients (43.3%). Five patients (16.7%) had minimal regression. The overall response rate as 66.7%. Median survival of all patients from start of treatment was 11.2 months. Median survival of responders and nonresponders was 12.4 months and 4.6 months, respectively (P less than 0.05). No differences in response rates, duration of response, or survival was seen between the two schedules. Drug toxicity was moderate to severe, but morbidity of HAI per se was minimal. Intermittent HAI of 5-FU and mito-C is a well-tolerated treatment modality associated with few serious complications. The response rate, duration of response, and the survival is comparable to continuous HAI infusion of 5-FU or floxuridine (FUDR). As given in this study, mito-C did not appear to provide added benefit.
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PMID:Hepatic artery infusion with 5-fluorouracil and mitomycin-C in metastatic colorectal carcinoma phase II study. 618 67

A prospective phase II evaluation of regional FUDR chemotherapy using a totally implantable drug infusion pump was conducted in 81 patients with colorectal metastases to the liver. The survival results were compared to a historical control group of 129 patients with isolated liver metastases. The two groups were comparable with respect to their dominant prognostic factors. The pump patients received their continuous chemotherapy on an outpatient basis and had an 88% response rate, as evidenced by a fall in their serum CEA levels by one-third or greater after two cycles of chemotherapy. By four criteria, the regional chemotherapy patients had an improved survival rate compared to the control series. First, the 1 year survival and median survival was better for the entire group of pump patients vs. controls (82% vs. 36%, 26 months vs. 8 months, p less than 0.0001). The survival for the regional chemotherapy patients was not influenced by the extent of tumor involvement, whether previous systemic 5-FU was given, or whether the patient had symptomatic disease. Second, the entire group of regional chemotherapy patients (including nonresponders) had a greater 1 year survival compared to the most favorable subgroup of control patients with the following characteristics: normal liver function tests, no symptoms, and only one lobe involved (82% vs. 66%, p = 0.009). Third, a subgroup of 49 pump patients, whose initial treatment for metastatic disease was regional chemotherapy (within 3 months of diagnosis) had a better 1 year survival than an exactly matched group of 49 control patients (67% vs. 30%, p = 0.000003). Fourth, the actuarial survival for all 81 pump patients was significantly better than predicted by a mathematical model constructed to predict the patient's clinical course based upon the seven dominant prognostic variables identified in a multifactorial analysis (82% survival at 1 year vs. 33% predicted survival). While liver metastases could be controlled in most patients, the major cause of death was tumor progression in extrahepatic sites, particularly lung metastases and abdominal carcinomatosis. Although it appears that regional chemotherapy with an implantable pump appears to prolong life by 12 to 18 months more than matched historical controls, these results must be confirmed by a randomized (phase III) prospective clinical trial.
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PMID:A prospective phase II clinical trial of continuous FUDR regional chemotherapy for colorectal metastases to the liver using a totally implantable drug infusion pump. 622 95

Metastatic cancer of the liver has a dominant influence upon survival despite the presence of metastasis in other sites. For patients with untreated liver metastases, the median survival after diagnosis is 75 days, and only 7% survived 1 year. Prognosis of hepatic metastasis is related to the extent of liver involvement, and various staging systems have been proposed (Table I.1). Hepatic metastases are quite resistant to conventional systemic chemotherapy. Surgical resection is the treatment of choice whenever possible, but the resectability rate is rather low and the surgical mortality relatively high. Patients with solitary metastasis and those with primary in the colon, especially females, have had the best results. Regional chemotherapy to the liver has the advantages of achieving higher local concentrations of drug, prolonging the contact of drug and tumor cells, and reducing systemic toxicity. Infusion catheter can be placed either percutaneously or directly at the time of celiotomy. Many reports show that hepatic IA infusion of chemotherapeutic agents (5FU or FUDR) can give favorable response in 55%-80% of the cases and can prolong survival in comparison with untreated patients or patients receiving systemic chemotherapy (Tables I.2 and I.3). Some investigators have added one or more other agents to improve the therapeutic results. For instance, patients who were refractory to 5FU or MMC given as a single IV drug responded to the combination infusion therapy. Evidence from animal and human studies have demonstrated that both primary and metastatic tumors in the liver receive their blood supply almost exclusively from the hepatic arterial system, whereas normal liver tissue has a double supply: the hepatic artery and the portal vein. Thus, deliberate ligation of the hepatic artery has been used as a treatment of metastatic tumors of the liver. From 1966 to 1981, some 518 patients were reported to have undergone this operation as compared to 2327 patients treated with hepatic IA infusion chemotherapy (Table I.4). Although selective necrosis of tumor nodules has been demonstrated after HAL, there is always a shell of viable malignant cells left at the periphery. Thus, several series have administered chemotherapeutic agents either to the distal hepatic artery or to branches of the portal vein to prevent tumor regrowth. Currently there is no definite evidence that HAL with added infusion chemotherapy to the liver gives better response and/or survival results than infusion chemotherapy via the hepatic artery only and/or via the portal vein branches. The availability of a totally implantable infusion pump represents a remarkable advance in long-term i
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PMID:Regional management of liver metastases. II. 636 71


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