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)

In vitro studies have documented the synergistic activity of interferon (IFN) and fluorouracil (5-FU) in human cancer cell lines, and recent clinical trials have demonstrated the efficacy of this combination in metastatic colon cancer. The current study was undertaken to evaluate the combination of IFN alpha-2a plus 5-FU in previously untreated patients with metastatic renal cell carcinoma. From May 1990 through August 1990, 14 patients with metastatic renal cell carcinoma were treated with 5-FU 750 mg/m2/day continuous infusion IV days 1-5, followed by weekly IV infusions of 5-FU 750 mg/m2 beginning on day 12. Patients concurrently received IFN alpha-2a 9 x 10(6) IU subcutaneously 3 times per week beginning on day 1. The median age of patients treated was 57 (range 38-80) with a median Karnofsky performance status of 90 (range 60-100). Sites of metastases included lung only in 6 patients, liver only in 1 patient, 1 patient had bilateral disease at presentation, and the remaining patients had multiple sites of metastases. The median duration of therapy was 2 months. The predominant toxicities seen were stomatitis, nausea, flu-like symptoms and neurotoxicity. The only grade IV toxicity observed was severe vomiting in 1 patient, though 5 patients discontinued therapy within 2 months because of poor subjective response. With a minimum follow-up of 13 months no objective responses were seen. Thirteen of the 14 patients have had progressive disease and 11 have died. The median time to progression was 2 months (range 0.5-6 months) and the median survival was 5 months (range 2-14.5 + months).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A phase II trial of interferon alpha-2A plus fluorouracil in advanced renal cell carcinoma. A Hoosier Oncology Group study. 142 32

UFT is given to the patients with digestive cancer from the time before operation to prevent intra- and post-operative cancer dissemination and metastases. UFT (400 mg/day in terms of tegafur) was given preoperatively for 1-6 days in 6 patients with gastric cancer and 13 with colorectal cancer. The interval between the last administration and the beginning of the operation was 3.9 +/- 1.5 hours (mean +/- SD). The concentrations of tegafur, 5-FU, and uracil in the blood collected at the time of tumor resection were 9.68, 0.017, and 0.08 microgram/ml, respectively. In the patients with gastric cancer 5-FU concentration was 5.5 times higher in the normal mucosa, 3.3 times in lymph nodes, and 10.7 times in the tumor tissues than in the blood. In colorectal cancer patients, also, the 5-FU concentration was 5.6, 8.3 and 20.8 times higher in the normal mucosa, lymph nodes, and the tumor tissue, respectively, than in the blood. The 5-FU concentration in gastric cancer and colorectal cancer tissues decreased with time after administration of UFT but remained above the effective concentration 1.5-7 hours after administration of 200 mg. The tissue concentrations of FT-207, uracil, and 5-FU were correlated with each other.
 ...
PMID:[Concentration of 5-fluorouracil in the blood and tissues of gastric and colo-rectal cancer patients after oral administration of UFT]. 144 83

Between 1985 and 1990, 50 patients with unresectable liver metastases from colorectal cancer and 34 subjects with metastases from gastric cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable prot system. A catheter was inserted into the hepatic artery via the left subclavian artery and was connected to the implantable injection port in each patient. 5-Fluorouracil (5-FU) at 330 mg/m2 per week (167 mg/m2 daily given continuously over the initial 3 months for colorectal cancer), Adriamycin (ADR) at 20 mg/m2 every 4 weeks and mitomycin C (MMC) at 2.7 mg/m2 every 2 weeks were given to all 34 patients with gastric cancer and to 31 of the colorectal cancer patients. The remaining 19 patients with colorectal cancer received 5-FU at 1,000 mg/m2 every week. As a rule the treatment was performed on an outpatient basis. The side effects and complications observed included myelosuppression (23%), hepatic arterial occlusion (21%), and gastroduodenal mucositis (12%), although no major toxicity was encountered. The response rate (CR+PR) among the evaluated patients as determined using CT scans was 67% for colorectal cancer and 73% for gastric cancer. The overall median survival was 12 months and 15 months, respectively. Good local control of liver metastases from the colorectal and gastric cancers was achieved by repeated hepatic arterial infusion chemotherapy employing an implantable port system without the need for hospitalization and without producing major toxicity. Thus, the implantable port system is very useful for the management of patients with unresectable liver metastases.
 ...
PMID:Management of patients with unresectable liver metastases from colorectal and gastric cancer employing an implantable port system. 145 67

A 52-year-old woman was diagnosed to have IIc+IIa-like advanced gastric carcinoma in the upper stomach by X-ray and endoscopic examination with biopsy. CT scan revealed swelling of the para-aortic lymph nodes which was taken to be evidence of metastases of the gastric carcinoma. The patient was considered to have surgically non-curative gastric carcinoma (Stage IV), and preoperative chemotherapy was initiated. The regimen consisted of CDDP 50 mg (day 1-2, drip), 5-FU 750 mg (day 2-7, drip) and UFT 400 mg (from day 8 to the day before operation, oral). About one month after initiating treatment, total gastrectomy with lymph node dissection was performed. Histopathological examination of the section of the primary tumor revealed that only a few cancer cell nests (poorly differentiated adenocarcinoma) remained in the muscle and subserosal layer. In all of the lymph nodes which were suspected to have metastases preoperatively, cancer cells completely degenerated into mucinous lakes or foam cell nests. No liver metastasis nor peritoneal dissemination was detected, and this case was judged to be stage II after chemotherapy.
 ...
PMID:[Case report of a successful stage reduction of gastric carcinoma preoperatively treated by combined chemotherapy of 5-FU(UFT) and cisplatin]. 146 48

The recently completed VA Cooperative Study (CSP #268) of induction chemotherapy (cisplatin/5-FU) and definitive radiation (6600 to 7600 cGy) for organ preservation in advanced (stage III or IV) laryngeal cancer demonstrated that, although larynx preservation could be achieved in 64% of randomized preservation could be achieved in 64% of randomized patients, overall survival rates were not improved over conventional treatment (surgery/postoperative radiation). Of 166 patients randomized to induction chemotherapy, 46 had N2 or N3 disease and were analyzed to determine the effectiveness of the organ preservation treatment strategy on control of neck disease and survival. The clinical response of neck metastases to induction chemotherapy was significantly associated with subsequent salvage neck dissection (P = .008). The overall death rate was increased (P = .014) and survival time decreased in patients with less than a complete response in the neck after chemotherapy (P = .15). This was related primarily to failure to control the disease in the neck. The overall survival of patients achieving a complete response in the neck was improved over the randomized group of N2 or N3 patients treated with primary surgery. The findings suggest that response of neck nodes should be assessed independently of primary tumor response in trials of organ preservation strategies using induction chemotherapy, and that failure to achieve a clinical complete response in the neck warrants planned early salvage neck dissection in order to achieve improved overall survival.
 ...
PMID:Effectiveness of salvage neck dissection for advanced regional metastases when induction chemotherapy and radiation are used for organ preservation. 149 57

A 42-year-old female was diagnosed as having sigmoid colonic carcinoma with multiple metastases in the liver. Following sigmoid colectomy and descending colostomy, a catheter was inserted from the right gastroepiploic artery to the proper hepatic artery. From the day of surgery 5-Fluorouracil was administered in doses of 250 mg/day continuously through a catheter over the 2-month period of hospitalization. After the patient was discharged, 250 mg/day of 5-Fluorouracil was administered at home using Vaxter Infusor according to a regimen of 10-day continuous infusion and subsequent 4-day rest. Five months after the initial operation, the serum CEA level decreased dramatically, and CT scan of the liver revealed the complete disappearance of the metastases. The patient underwent a second operation in which the colostomy was closed, and she is doing well at this writing. This case suggests that long-term, ambulatory, continuous and intra-hepatic-arterial infusion of 5-Fluorouracil can be a very effective treatment not only in reducing the hepatic metastases but also in improving the quality of life of patients with colonic carcinoma.
 ...
PMID:[A case report of metastatic colonic carcinoma in the liver effectively treated by long-term, ambulatory and continuous, intra-hepatic-arterial infusion of 5-fluorouracil using disposable multi-day-type infusor]. 151 31

Out of 79 cases dealt with reservoir, a response was obtained in 31% of 51 assessable cases. When assessed by cumulative survival with Kaplan-Meier method, the 50% survival was 8 months for total cases and prolonged to 21 months for responsive cases. However, eventually re-hospitalization was required for almost all cases. Although oral nutrition was impossible because of poor general condition, there were many patients who refused re-hospitalization and wished to continue treatment at home. In the present study, in 5 such cases the usefulness of home parenteral nutrition (HPN) combined with chemotherapy was determined. All the five patients in this study had gastric cancer with metastases and recurrent lesions in the liver or lymph node, or localized or with peritoneal spread. The site of the reservoir was within the artery in 4 cases and in the abdominal cavity in 1 case. The chemotherapy was multidrug-combination therapy consisting of 5-FU, MMC, CDDP and EPIR. In 4 cases local hyperthermia was added. In 3 out of the 5 cases (3 out of 7 lesions), a partial response (PR) was obtained. The mean dwelling period of the reservoir was 349.2 days for all cases, but longer than 400 days for 3 cases in which PR was obtained. For HPN, a catheter was inserted through the internal cervical vein, and 750-1,500 kcal/day was administered intermittently during night or constantly for 24 hours. In cases in which PR was obtained with chemotherapy and in those in which the reservoir for HPN was been in place before the terminal stage, the reservoir could be used for administration for a prolonged period. The mean dwelling period of the reservoir was 179.8 days and the duration of home stay was 121.2 days. All of the patients were classified as PS2 or higher and pronounced improvement in PS was obtained after HPN in only 1 case. Four out of the 5 patients were satisfied with receiving treatment at home. However, since HPN is associated with many problems such as sudden worsening in general condition, cancer pain and great burden to families, the solution to these problems remains.
 ...
PMID:[Evaluation of loco-regional cancer chemotherapy with assistance of home parenteral nutrition]. 153 Mar 38

Hepatic regional treatment represents an attempt to improve tumor response by increasing drug concentration with low systemic toxicities. Recently in vitro and clinical studies have shown that the cytotoxicity of 5-fluorodeoxyuridine (FUDR) and 5-fluorouracil (5FU) can be potentiated by high doses of leucovorin (LCV). Two pilot studies with intraarterial FUDR, 5FU, and LCV were initiated. Since 1982, 221 patients with colorectal liver metastases were treated by various forms of long-term monthly continuous regional treatment using implantable ports or pumps. FUDR (0.05 to 1.7 mg/kg/d) was administered alone or combined with 5-FU and leucovorin. In 61 patients curative liver resection was possible and was followed by adjuvant arterial treatment. Overall median survival time (MST) was 15 months and increased to 36 months after liver resection. This was influenced by the following important factors: treatment, number of metastases, extent of infiltration, tumor volume, and minimal intraoperatively diagnosed extrahepatic disease. The response rate varied from 69% to 23%. Time of development of extrahepatic progression was not delayed by additional systemic treatment. Local side effects significantly depended on the duration of arterial infusion. The rate of biliary sclerosis ranged from 19% to 0%. Occurrence of chemical hepatitis was between 7% and 38%. In contrast, after combined intraarterial treatment with LCV, systemic side effects, mainly stomatitis and diarrhea, were dose limiting. Despite the improvement of survival after regional treatment, further randomized trials are mandatory to compare regional with relevant systemic treatment.
 ...
PMID:Continuous regional treatment with fluoropyrimidines for metastases from colorectal carcinomas: influence of modulation with leucovorin. 153 72

The inhibition of thymidylate synthase (TS) by the fluorouracil (5-FU) metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) is considered to be one of the main mechanisms of action of 5-FU. The inhibition of TS is mediated by the formation of a ternary complex between TS, FdUMP, and the folate cofactor 5,10-methylene tetrahydrofolate. The activity of TS, its inhibition by FdUMP, and the binding of FdUMP to TS have been determined in biopsy specimens of colorectal tumors, liver metastases, normal colon mucosa, and liver obtained from patients who never had received chemotherapy, and patients treated with 5-FU or 5-FU with leucovorin (LV). In nontreated patients we observed a large variation in the activity of TS both at 1 microM and 10 microM dUMP (40- to 80-fold difference). In contrast, in normal colonic mucosa this variation was less than 10-fold. FdUMP binding in tumors also varied considerably but was not detectable in normal mucosa. The deviations from normal (ie, as found in mucosa) kinetic patterns of TS may represent a mutant TS form. Thirty-five patients with advanced colorectal cancer received 5-FU (500 mg/m2) at 1 to 48 hours prior to surgery. In biopsy specimens of tumor and normal tissues the residual catalytic activity of TS and the percentage of free-binding sites for FdUMP (TS-free) were determined. After dissociation of FdUMP, total catalytic activity of TS- and total FdUMP-binding sites (TS-tot) were determined. Total and residual catalytic TS activity in primary tumors and metastases showed a large variation. TS-tot and TS-free in tumors also varied considerably. At least eight patients with an undetectable TS-free showed response to subsequent intraarterial treatment with 5-FU. To several patients leucovorin (2-hour infusion of 500 mg/m2) was administered with a 5-FU bolus (500 mg/m2) in the middle of the infusion. Biopsy specimens were obtained about 48 hours after treatment. In these patients inhibition of TS was markedly enhanced compared with patients who did not receive LV. The large variation in TS may be related to the observed variation in clinical response to 5-FU treatment.
 ...
PMID:Time course of inhibition of thymidylate synthase in patients treated with fluorouracil and leucovorin. 155 55

The prognosis of colon cancer after curative resection is mainly related to the onset of metastases, and especially of liver metastases. In order to prevent metastatic recurrences, the value of adjuvant medical therapy is widely admitted. The aim of the present review was to analyse the conclusions of the main recent randomized trials assessing the comparative value of different adjuvant protocols. The results obtained using either classic systemic infusion or intraportal infusion, which is mainly used with the intent of preventing liver metastases, are reported. At term of this review, we conclude that: adjuvant chemotherapy using combined drugs (5-Fluorouracil + Methyl CCNU, 5-Fluorouracil + Oncovin) did not prove to be more active than 5-FU alone. the beneficial action of a combined 5-FU + Levamisole regimen has been clearly demonstrated for patients with a Dukes C tumor. intraportal adjuvant therapy has been shown to be effective for patients with Dukes B tumors in only one limited trial but this remains to be confirmed. On the basis of the present data, new adjuvant programs using combined chemotherapeutic and immunotherapeutic compounds, and combined systemic and regional infusion, can be envisaged.
 ...
PMID:[Does an efficacious adjuvant treatment exist in resected colonic carcinoma?]. 158 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>