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)

We have investigated the effect of a combined chemoimmunotherapy protocol with liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE), 5-fluorouracil (5-FU), and 5-formyltetrahydrofolate (leucovorin) on the growth of hepatic metastases using carcinoma H-59, a liver-homing subline of the Lewis lung carcinoma (P. Brodt, Cancer Res., 46: 2442-2448, 1986). C57BL/6 mice inoculated with the tumor cells via the intrasplenic route received three i.v. injections of liposomal MTP-PE, the first of which was administered 3 days prior to tumor cell inoculation. Chemotherapy with 5-FU and leucovorin at the maximal tolerated doses (30 mg/kg per injection) was initiated immediately after tumor inoculation and continued on alternate days for a total of 4 injections. The incidence of liver metastases in animals which received the combined therapy was compared to that in animals treated with chemotherapy or immunotherapy alone. We found that while the number of liver metastases was reduced in all of the treatment groups as compared to control untreated or placebo-treated animals, the combined effect of 5-FU leucovorin and liposomal MTP-PE was significantly better than that of chemotherapy or immunotherapy alone. This was reflected in a reduced incidence (70% as compared to 100% in all other groups) and in a significant reduction in the number and size of the liver nodules. Our results suggest that the efficacy of 5-FU and leucovorin in the treatment of hepatic metastases could be significantly augmented by the addition of the liposome-encapsulated immunoadjuvant MTP-PE.
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PMID:Eradication of hepatic metastases of carcinoma H-59 by combination chemoimmunotherapy with liposomal muramyl tripeptide, 5-fluorouracil, and leucovorin. 142 70

Drug therapy is most often used in colorectal cancer for palliation of metastatic disease. Current data also support the use of adjuvant chemotherapy following complete surgical resection in patients with locoregional lymph node metastases. The agent most widely used in the treatment of colorectal cancer is the antimetabolite fluorouracil (5-fluorouracil; 5-FU). This fluoridated pyrimidine has been available for over 30 years, yet to date no other single agent has proven to be more efficacious. Controversy exists about the most desirable schedule for administration of fluorouracil. Efforts have been made to improve upon its therapeutic index and efficacy by using the concept of biomodulation, in which chemicals which are not themselves active antineoplastic agents against colorectal cancer are administered with fluorouracil in an attempt to enhance the sensitivity of the cancer cell to fluorouracil. Biomodulation agents currently in use in clinical practice include leucovorin (calcium folinate), methotrexate, and interferon-alpha. Other biomodulation strategies are currently under investigation. Adding putatively active antineoplastic agents to fluorouracil to form combination chemotherapy regimens has not yielded convincingly superior results to treatment with fluorouracil alone, and the toxicities of many of these combination regimens have been formidable. Secondary therapies following failure of fluorouracil-based regimens have been similarly disappointing. Current areas of investigation into the chemotherapy of colorectal cancer include development of new agents, locoregional administration of chemotherapy, and manipulation of intrinsic drug resistance mechanisms of the cancer cells.
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PMID:Drug treatment of colorectal cancer. Current status. 172 64

A total of 20 patients with advanced pancreatic adenocarcinoma were enrolled in a phase II trial testing the activity of 5-fluorouracil given at 370 mg/m2 as a rapid i.v. bolus for 5 consecutive days, preceded by a rapid i.v. bolus of 200 mg/m2 5-methyltetrahydrofolic acid. The treatment was repeated every 4 weeks. The median age of the patients was 68 years and their median Eastern Cooperative Oncology Group (ECOG) performance status was 1. There were 7 patients with locally advanced disease and 13 with distant metastases (median, 2 sites). A median of 3 monthly cycles of treatment (range, 1-7) were given, with a corresponding dose intensity of 396 mg/m2 per week (86% of that planned). No complete response, 1 partial response, and 8 cases of disease stabilization were obtained. In general the regimen was well tolerated, with only 2 patients suffering from grade 3 stomatitis or diarrhea; the most common toxicity was nausea, which was experienced by almost 50% of the patients. The combination of 5-methyltetrahydrofolate plus 5-fluorouracil appears as little effective in this disease as 5-fluorouracil plus 5-formyltetrahydrofolate (leucovorin). It is suggested that bolus 5-fluorouracil is so inactive as an "effector agent" against pancreatic cancer that its biochemical modulation with exogenous high-dose reduced folates cannot improve the therapeutic outcome produced by the fluoropyrimidine in these patients.
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PMID:5-Fluorouracil plus 5-methyltetrahydrofolate in advanced pancreatic cancer. GLISP (Gruppo Ligure Studio Pancreas). 782 78

The scientific documentation for fluorouracil-based chemotherapy in patients with colorectal cancer has increased during recent years, both for the adjuvant primary situation and in recurrent and metastatic disease. In the case of operable colorectal cancer (stage Dukes B and C), the patients should be included in the ongoing randomized trial on use of fluorouracil and levamisol. In advanced disease, fluorouracil combined with calcium folinate may have palliative effects in terms of relief of symptoms, improved quality of life, delay of onset of symptoms and probably also prolonged survival in 40-50% of the patients, without serious toxicity. In many cases, however, the patient should not be given chemotherapy.
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PMID:[Chemotherapy in colorectal cancer. Recommendations of the Norwegian Gastrointestinal Cancer Group]. 863 62

Colorectal carcinoma is one of the most common cancers in Western countries (yearly incidence rate of 1:3000), and represents, after lung cancer, the second leading cause of deaths due to cancer. During the past decades, knowledge about this carcinoma has considerably increased, but little progress has been made in improvement in patient survival. At least 40% of patients with colorectal cancer will have metastases sometime during the course of their illness. In colon cancer, the first therapeutic approach is surgery, but the important role of adjuvant chemotherapy in these patients, in terms of disease-free survival and overall survival benefit, is now well established. Until today, standard therapy was represented by fluorouracil plus levamisole and/or calcium folinate (folinic acid). Other strategies are represented by monoclonal antibodies (mAb), which improve survival, (with a decrease in mortality by 32%), and by portal vein fluorouracil, alone or in combination with systemic therapy. In rectal cancer, the best results have been obtained with a combination of radiotherapy and chemotherapy. In advanced colorectal cancer, a standard treatment has not yet been established. This disease is usually considered as poorly chemosensitive and for more than 30 years fluorouracil has been the standard drug. Tumour response rates (partial+complete) for patients treated with bolus intravenous fluorouracil are 10 to 15%, with a median survival about 1 year. Many attempts have been made to improve these results. Biochemical modulation of fluorouracil is one of the most interesting strategies developed in the last few years in an attempt to increase the therapeutic index of this compound. Another way has been to administer fluorouracil by continuous infusion. Further innovative compounds such as irinotecan and raltitrexed are now being evaluated in clinical trials. Preliminary data from phase II and III studies have provided encouraging results on the use of these new drugs. In metastatic disease confined to the liver, the possibility of locoregional therapy through implantable pumps should be taken into consideration.
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PMID:Treatment of colorectal cancer. Current guidelines and future prospects for drug therapy. 909 62

This phase I trial combining UFT plus oral calcium folinate (Orzel) with irinotecan (CPT-11) (Camptosar) for the treatment of patients with advanced or metastatic colorectal cancer will open shortly. Eligible patients will have locally advanced or metastatic colorectal cancer, and they may have received adjuvant chemotherapy (provided it has been completed more than 6 months prior to study entry), but will have not received any chemotherapy for advanced or metastatic disease. The primary objectives of this study will be to determine the side-effect profile, dose-limiting toxicities, and the maximum tolerated dose of this combination. A recommended starting dose for future trials will be defined. Response rates will also be observed as a secondary objective. The first cohort of six patients will receive irinotecan 200 mg/m2 by intravenous infusion over 90 minutes on day 1 (the schedule that is in general use in Europe). On days 1 to 14, patients will receive UFT 250 mg/m2/d and calcium folinate 90 mg/d, both divided into three equal doses. This will be followed by a 1-week rest period with treatment for the next cycle resumed on day 22. In subsequent cohorts of six patients, UFT and irinotecan will in turn be escalated provided toxicity is acceptable. The calcium folinate dose will remain fixed at 90 mg/d throughout. The maximum tolerated dose is defined as that at which dose-limiting toxicities occur in more than one third of patients. The cohort of patients treated at the dose below the maximum tolerated dose will be expanded to a total of 20 patients to fully define the pattern of toxicities and activity of the combination.
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PMID:UFT plus calcium folinate/irinotecan in colorectal cancer. 1044 62

Locally advanced or metastatic adenocarcinoma of the stomach still carries a poor prognosis, with 5-year survival rates of < 15%. Palliative chemotherapeutic regimens for this disease are largely 5-FU-based. We have investigated the clinical activity of an oral combination of uracil and tegafur (UFT) with calcium folinate (Orzel), in patients with measurable metastatic disease. Thirty-six patients received a total of 94 courses of daily UFT 300 mg/m2 plus calcium folinate 90 mg for 28 consecutive days followed by a 7-day rest. Planned treatment doses were maintained in 83% of all evaluable courses. Main toxicities included diarrhea (21 patients) and nausea and vomiting (20 patients). Other side effects were asthenia, malaise, stomatitis, and myelosuppression. At present, 26 patients are evaluable for response. Of these, one achieved a complete response and three achieved partial remissions. In addition, six patients reached stable disease, yielding an overall response rate of 27%. We conclude that the combination of UFT and calcium folinate is a feasible outpatient regimen that warrants further clinical evaluation.
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PMID:UFT and oral calcium folinate as first-line chemotherapy for metastatic gastric cancer. 1044 64

Protracted infusions of 5-fluorouracil (5-FU) combined with pelvic radiotherapy have been associated with improved survival and decreased local and distant metastases in the adjuvant therapy of rectal cancer. However, this method of 5-FU infusion requires the inconvenience and expense of central venous line placement and care, infusion pumps, and treatment of catheter-related complications. We previously demonstrated that a completely oral therapy with UFT (uracil plus tegafur in a 4:1 molar ratio) plus oral calcium folinate (Orzel) can achieve pharmacokinetic parameters similar to those associated with protracted 5-FU infusions. This trial examines the feasibility of using UFT plus oral calcium folinate both during preoperative pelvic radiation and postoperatively, and shows that patients can be treated safely and effectively with a completely oral chemotherapy program combining UFT plus oral calcium folinate with pelvic radiation therapy.
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PMID:Preoperative UFT and calcium folinate and radiotherapy in rectal cancer. 1044 82

We performed FOLFOX 4 therapy in a patient with lung metastasis (a 62-year-old woman) after surgery for rectal cancer and observed both normalization of tumor markers and disappearance of the metastasis. Low anterior resection was performed for progressive rectal cancer, and treatment with UFT and folinate was started one month after surgery. However, tumor markers increased after 2 months of treatment and CT scans showed metastases to both lungs. FOLFOX 4 therapy was started, and tumor markers became normal after four courses, while the lung metastases disappeared after 10 courses. The dosage of FOLFOX 4 was reduced after three courses due to neutropenia and diarrhea. This treatment appeared to be effective for the inhibition of lung metastasis associated with colorectal cancer.
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PMID:[A patient with recurrent rectal cancer in whom pulmonary metastasis disappeared by FOLFOX 4 therapy]. 1803 29

A 78-year-old man was admitted to our institute with the symptom of melena. The patient was diagnosed as having advanced rectal cancer (T4N2M1) with multiple bone metastases. Chemoradiation therapy was chosen for the local control because our proposal of colostomy was rejected. Concurrent chemoradiation therapy [46 Gy/23 Fr+tegafur/uraci (l UFT 400 mg/m2)/calcium folinate (Leucovorin: LV 75 mg/body)] resulted in a good partial response and the patient became asymptomatic. UFT/LV were administrated and most of the bone metastases were diminished. After 3 years of disease remission with good quality of life, local tumor recurred with the symptoms of melena and bowel obstruction. Colostomy and additional radiotherapy were performed for the palliation. He died after 4 years from the initial treatment. In advanced rectal cancer with distant metastases, chemoradiation therapy for local control plus systemic chemotherapy could be an alternative to improve quality of life.
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PMID:[Successful chemoradiation therapy for local control of rectal cancer with multiple bone metastases--a case report]. 2003 28


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