Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a non-randomized pilot study, 10 patients with histological proof of metastatic colorectal adenocarcinoma were treated by hyperthermia/chemotherapy protocol (41,8 degrees C and 1000 mg 5-FU). Plasma levels of 5-FU were determined after single dose at normothermia and hyperthermia. Plasma concentration time course was consistent with a two-compartment pharmacokinetic open model, with first order kinetic and was significantly altered by hyperthermic treatment. Cytotoxicity of 5-FU was substantially enhanced at hyperthermia (41.8 degrees C) as judged from the clonogenic surviving fractions from established human colon cancer cell lines. Our in vitro and in vivo results suggest that whole body hyperthermia combined with 5-FU is an active combination to develop further in the treatment of colorectal carcinomas.
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PMID:The effect of whole body hyperthermia on 5-fluorouracil pharmacokinetics in vivo and clonogenicity of mammalian colon cancer cells. 671 74

Forty patients with gastric cancer and 30 patients with colon cancer were administered FT-207 prior to the operation. The relation between a total dose (4-88g) and tissue concentration of 5-FU was investigated and the following results were obtained. (5-FU concentration was measured with the method of Gas chromatography mas fragmentography) 1) The relation between total doses of FT-207 (x) and concentration of 5-FU in the tissue (y) was demonstrated by the formula: y = 0.00317x + 0.025 (gastric cancer) r = 0.519, p = 0.0001 y = 0.0019x + 0.043 (colon cancer) r = 0.641, p = 0.0001 2) In most of the patients with rectal cancer who received radiation therapy prior to the operation, 5-FU concentration in the tissue was extremely low. 3) 5-FU concentration showed no difference between the normal and metastatic lymph nodes, or among the lymph node groups. Administration methods (oral intake or suppository) had no influence on the concentration of 5-FU. 4) Among the organs, 5-FU concentration was higher in the following orders: liver, normal mucosa, lymph node, tumor, normal serosa. 5) In five autopsy cases, 5-FU concentration of the tissue show a great difference among them, and some cases showed 10 times as high concentration as others in the tissue of every organ.
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PMID:[Tissue concentration of 5-FU following pre-operative administration of FT-207]. 682 Sep 12

5-Fluorouracil (5-Fu) was administered by a constant venous infusion schedule at a dose of 300 mg/m2/d for 30-180 days. The dose schedule was associated with minimal toxicity in 32 patients with gastrointestinal cancer treated by employing a portable infusion pump for ambulatory drug delivery. Cumulative dose of 5-Fu was extended to three to four times that achieved by intermittent bolus therapy or short-term 5-day infusion therapy. Objective tumor regression was observed in six of 22 patients with measurable disease; 10 patients had stable disease, five of whom had a decrease in CEA levels. The responses according to tumor type were as follows: 1/1 gastric cancer; 1/2 hepatoma; and 4/18 colon cancer. The superiority of this new treatment schedule for 5-Fu will need to be established by prospective randomized clinical trials.
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PMID:Protracted ambulatory venous infusion of 5-fluorouracil. 683 1

Survival rates for patients with colorectal cancer have remained unchanged during the last 30 years. Every third patient with colon cancer Dukes' C and every fourth patient with rectal cancer Dukes' C survives 5 years. Of the patients who succumb to colorectal cancer, 85% will die within 3 years from diagnosis. There are many studies concerning the mechanisms of adjuvant chemotherapy. Its effectiveness has been proven in animal experiments. Micrometastases have a large growth fraction, few non-proliferative cells, and because of this, increased sensibility to cytostatics. Adjuvant chemotherapy aimed at treating occult metastases. In colorectal cancer the combination of 5-FU and Nitrosurea has been shown to have a better effect than 5-FU alone. Grage et al. have shown patients with colorectal cancer Dukes' C to have a longer tumour-free interval with adjuvant 5-FU, and this treatment gives patients with rectal cancer a prolonged survival time. In an adjuvant study, peroral 5-FU 90 days versus placebo did not show any effect. In another adjuvant study Vincristin, CCNU and 5-FU treated patients had fewer tumour recurrences than control patients. The observation time is, however, rather short. Adjuvant chemotherapy for colorectal cancer has shown promising results and it is hoped that further attempts with other forms of cancer in the gastrointestinal tract will also yield the same results.
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PMID:[Background and experience of adjuvant cytostatic therapy in gastrointestinal cancer (author's transl)]. 703 99

Fifty-seven patients were treated with continuous infusion of PALA at a dose of 850 mg/m2/day x 5 and iv bolus injection of 5-FU at a dose of 300 mg/m2/day x 5, which was given at the end of each 24-hour PALA infusion; the treatment interval was 28 days. The overall response rate among 43 evaluable patients was 14%. Two of 21 patients (10%) with colorectal carcinoma, two of eight patients with pancreatic carcinoma, and two of four patients with breast carcinoma achieved partial responses lasting 2-12 months. One of the responding patients with colon cancer and two with breast cancer had failed to respond to prior therapy with 5-FU; one of the responding patients with breast cancer had previously received an inadequate trial of a similar regimen. Toxic effects were mild to moderate and were confined to oral mucositis in most patients. It is concluded that this regimen offers little enhancement of the antitumor activity of 5-FU in patients with colorectal cancer previously treated with 5-FU. Investigation of other infusion techniques for the PALA and 5-FU combination is recommended, with particular attention to the treatment of colorectal, pancreatic, and breast carcinomas.
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PMID:Phase II trial of combination therapy with continuous-infusion PALA and bolus-injection 5-FU. 705 15

The Southwest Oncology Group conducted a phase II study of anguidine in 134 patients with gastrointestinal malignancies. Anguidine was administered as a 4-hour infusion at doses of 3.0 and 4.5 mg/m2 daily x 5. Response rates for patients with colon carcinoma were 22% (four of 18 patients without previous chemotherapy) and 6% (four of 63 patients with previous chemotherapy). There were no responses in patients with pancreatic cancer (four patients) or gastric cancer (six). Toxic effects included thrombocytopenia (19.8%), leukopenia (18.8%), nausea and vomiting (49%), hypotension (37%), and confusion (12%). Antitumor activity of anguidine in patients with colon cancer may be similar to that of 5-FU, but nonhematologic toxicity is substantial.
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PMID:Phase II study of anguidine in gastrointestinal malignancies: a Southwest Oncology Group study. 705 20

Concurrent administration of allopurinol allows escalation of 5-FU doses in man when 5-FU is given by continuous infusion for 5 days. Forty-nine patients received 81 courses of treatment with 5-FU and allopurinol in phase I and II trials. The dose-limiting toxicity was mucositis; marrow toxicity was mild. Neurotoxicity, possibly related to 5-FU, occurred in eight patients. No responses were seen in 14 evaluable patients with colon cancer, 11 of whom had had prior 5-FU. One patient with Hodgkin's disease had a partial response; one patient with diffuse histiocytic lymphoma had transient disease regression. Although allopurinol does modify the toxicity of 5-FU, permitting dose escalation, it does not increase the therapeutic index in colon cancer. Infusional 5-FU deserves further study in lymphoma.
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PMID:5-FU and allopurinol: toxicity modulation and phase II results in colon cancer. 708 15

Many studies reported the pretreatment with methotrexate followed by 5-FU resulted in the greatest tumor cell killing. Our preliminary laboratory studies confirmed the possibility of drug synergism in the L1210 cell line, but not in human bone marrow cells. Thirteen patients with metastatic adenocarcinoma of the breast and seven patients with metastatic adenocarcinoma of the colon were treated with an innovative approach in which methotrexate preceded 5-FU administration in an attempt to cause drug synergism and prevent drug antagonism. All patients with breast cancer and two patients with colon cancer had been extensively pretreated with multiple drugs. Of the cancer patients so treated, three (23%) with breast cancer and two (28%) with colon cancer demonstrated objective tumor response. In addition to these patients, six (46%) with breast cancer and three (43%) with colon cancer demonstrated subjective improvement as manifested by total pain relief and reduction in CEA titer. The preliminary results reported in this study suggest that sequential utilization of intermediate doses of methotrexate, followed by high doses of 5-FU, is an effective combination chemotherapy for patients with breast and colon malignancies.
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PMID:Effectiveness of intermediate-dose methotrexate and high-dose 5-fluorouracil as sequential combination chemotherapy in refractory breast cancer and as primary therapy in metastatic adenocarcinoma of the colon. 744 20

Combination chemotherapy with FUra and LV has been reported as a useful treatment for patients suffering from colon carcinoma. Usually, both FUra and LV are administered by intravenous infusion, but not orally. UFT, an anti-neoplastic agent consisting of FT and uracil, is widely used for oral administration in Japan. Using human tumor xenografts of 10 cell lines, we evaluated the efficacy of UFT combined with l-LV, which is the active form of LV, by oral administration. Combined treatment of UFT with l-LV was more effective than UFT alone on the growth suppression of colon carcinoma (KM 20 C, Col-1) and mammary carcinoma (H-31, MX-1). When 1.85 mg/kg (5.55 mg/m2) of LV was given to tumor bearing mice, the antitumor activity of UFT was augmented and at a dose of 5.56 mg/kg (16.7 mg/m2) of LV, it was significantly augmented. Among various 5-FU derivatives, such as UFT, 5'-DFUR or FUra, combined treatment using UFT with l-LV was the most effective by oral administration. l-LV did not improve the anti-tumor efficacy or toxicity of 5'-DFUR. l-LV seemed to augment the anti-tumor activity of FUra, but not significantly. These results suggest that combination chemotherapy of UFT with LV is a promising approach for the clinical treatment of human colon cancer.
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PMID:[Augmentation of chemotherapeutic efficaciousness of UFT by oral l-leucovorin--growth-inhibitory activity of combination against human tumor xenograft]. 748 21

After many years of negative trials of adjuvant chemotherapy in colon cancer, two studies in the years 1989 and 1990 of the NCCTG and the Intergroup Trial, respectively showed a significant reduction of relapse and improved survival in patients treated with 5-FU and levamisole in an adjuvant setting. The absolute and relative reductions in 5-year-relapse and death rates were approximately 35% and 17%, respectively. Intraportal perfusion of the liver in an adjuvant perioperative setting seems to be of similar benefit. Preliminary data of the adjuvant therapy with 5-FU and folinic acid also show that this combination seems to have at least the same efficacy as the current standard 5-FU/levamisole in the adjuvant therapy of colon cancer. At the current time, patients with colon cancer of Dukes stage C should be offered adjuvant chemotherapy with 5-FU/levamisole outside of clinical studies.
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PMID:[Adjuvant treatment of colonic carcinoma]. 750 18


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