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)

The usefulness of preoperative administration of Doxifluridine (5'-DFUR) for treating carcinoma of the colon and rectum was studied through a determination of 5-FU concentration in carcinoma, normal intestine, serum and lymph nodes concerned. 1,200 mg/day of 5'-DFUR was administrated orally to 16 patients with carcinoma of the colon and rectum over four days before surgery, and the specimens obtained by resecting the carcinoma were subjected to the mass spectrometry using a gas chromatography to determine 5-FU concentrations. The time needed for collection of the specimen from the final administration of 5'-DFUR was 3.0 to 20.5 hours (10.7 +/- 6.6 hrs). 5-FU concentrations were as follows: 75.8 +/- 61.2 ng/g in the carcinoma, 39.9 +/- 63.5 ng/g in the normal intestine and 26.8 +/- 52.4 ng/g in the lymph nodes concerned, which were significantly high as compared to serum level of 2.3 +/- 4.9 ng/ml (p less than 0.05). Further, a high level of 90.1 +/- 29.3 ng/g (n = 6) of the carcinoma was sustained even at 12 hours or more since final administration of 5'-DFUR. In view of histological patterns, the levels were 139.5 +/- 69.5 ng/g (n = 5) in well differentiated carcinoma and 46.9 +/- 27.4 ng/g (n = 11) in moderately differentiated carcinoma, the level being significantly high in the former (p less than 0.05). A histologic therapeutical effect was shown in one out of 16 cases, with the improvement that remained the score to grade 1. This was deemed due to the small dosage and a short duration of 5'-DFUR.
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PMID:[A study on preoperative administration of doxifluridine in carcinoma of the colon and rectum]. 213 72

Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.
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PMID:Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02. 239 56

Recombinant interferon alfa-2a (rIFN alpha-2a) synergistically augments the cytotoxic effects of the antimetabolite fluorouracil (5-FU) against two human colon cancer cell lines. A pilot clinical trial was initiated to determine whether this same combination of agents would show clinical utility greater than that expected with 5-FU alone in patients with advanced colorectal carcinoma. 5-FU was administered at 750 mg/m2/d for 5 days as a continuous intravenous infusion followed by weekly bolus therapy. rIFN alpha-2a was administered at 9 million units subcutaneously three times per week starting on day 1. Doses of 5-FU were modified for mucosal toxicities and myelo-suppression, and doses of rIFN alpha-2a were modified for fatigue and neurologic toxicities. Thirty-two previously untreated patients with advanced colorectal carcinoma were entered into a clinical trial. With the exception of one patient with a destructive lesion of the sacrum, all patients had metastases to visceral organs, abdominal wall, or pelvis. Twenty patients (63%) achieved a partial response, seven remained stable, and five had progressive disease. Mucosal toxicities limited delivery of full projected dose. Two patients died following episodes of watery diarrhea progressing to sepsis. A third died suddenly, secondary to an interstitial pneumonitis. The remainder of the toxicities were managed with dose reductions. At the median follow-up of 8 months, 23 of 32 patients remain alive. Nine are alive at 16 to 30+ months. The early results of this single-institution study are promising, but will require confirmation in a multi-institutional setting currently being conducted by the Eastern Cooperative Oncology Group.
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PMID:Clinical update on the role of fluorouracil and recombinant interferon alfa-2a in the treatment of colorectal carcinoma. 240 91

K18 is a new drug produced by a combination of Melphalan and human immunoglobulin. K18 produced an inhibitory effect on the proliferation of human gastric and colon cancer transplanted in to nude mice. Also, combination effects of K18 with MMC and 5-FU were recognized in the same system. In a study of distribution after K18 administration, the accumulation and retention of this drug in the tumor region were observed. In the case of Melphalan administration, these phenomena were not observed. The antitumor activity of tumor homogenate was evaluated using a colony-forming assay with KB cells. As to the Melphalan-treated group, a four-hour homogenate reduced the number of colonies but a 48-h one did not. In the K18-treated group, the four-hour homogenate decreased the number slightly and the decrease became obvious with 48-h homogenate. In cell cycle analysis using K18 or Melphalan administration, gathering of S-phase cells was observed, but these changes appeared later with K18 than with Melphalan. This result showed that the effect of K18 was produced by the alkylating activity of Melphalan which was combined with immunoglobulin. For clinical application, K18 was administered to cancer patients at a dose of 60-90 mg every day. Two cases of good response were achieved. No side effect was observed. This remarkable efficacy and low degree of side effects in clinical application is probably due to the higher affinity and accumulation of K18 in the tumor region. K18 is a useful new drug for clinical application alone, or in combination with other chemotherapeutic drugs.
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PMID:[A study of the antineoplastic activity of K18]. 242 38

We reported 2 patients treated with Methotrexate (MTX)-Fluorouracil (5-FU) sequential therapy combined with Doxifluridine (5'-DFUR). The method of administration was as follows: MTX 60 mg was given intravenously (iv) followed by 5-FU 600 mg iv 2 hours later in colon cancer and 5 hours later in gastric cancer. Leucovorin 20 mg was administered 3 times every 6 hours beginning 6 hours after 5-FU infusion. This cycle was repeated once a week for 5 weeks. 5'-DFUR 1,200 mg was given orally daily and continued after MTX.5-FU therapy. Patient 1 was a 60-yr-old female with recurrent colon cancer developed four years after sigmoidectomy. She was referred to our hospital for further examinations of elevated serum carcinoembryonic antigen (CEA). The enlarged intraabdominal lymph nodes due to recurrence were demonstrated on computer tomography and the chemotherapy was performed as described above. The swelling of lymph nodes showed marked reduction in size and CEA value was normalized. Patient 2 was a 59-yr-old man with advanced gastric cancer accompanied by giant liver metastasis. Both primary and metastatic lesion responded favorably to this regimen. There was no remarkable side effect in either patient. These results suggest that this method is worth performing in further clinical trials for cancer patients.
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PMID:[Two cases of gastrointestinal cancers with major responses to sequential methotrexate 5-FU plus 5'-DFUR]. 252 5

Several different strategies to improve the in vitro cytocidal effect of 5-fluorouracil/leucovorin (5FU/LV), including modulation of dosage and schedule and combination with other cytotoxic agents or biochemical modulators, were examined in the COLO 320DM and Ht-29 cell lines by means of the Bactec system. Modest enhancement of 5FU activity by coadministration of LV was observed in both human colon cancer cell lines. Neither increased concentrations of LV nor prolonged drug exposure or preincubation with LV were found to enhance significantly the growth inhibitory activity of combined 5FU/LV. The only parameter that was found to affect the killing potential of the combination was the concentration of 5-FU, suggesting that lower doses of the antimetabolite would be more effective (COLO 320DM: P less than 0.003; Ht-29 P less than 0.02). The addition of either cisplatin, hyaluronidase or dipyridamole to 5-FU/LV yielded synergistic growth inhibition in 3/6, 2/6 and 2/6 human colon cancer cell lines, respectively. Strictly additive effects were noted for the combination with BCNU as well as concurrent exposure of the cells to 42 degrees C hyperthermia. Whether or not certain combined 5FU/LV drug regimens will result in an improved therapeutic index, however, remains to be determined in properly designed clinical trials.
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PMID:A study of various strategies to enhance the cytotoxic activity of 5-fluorouracil/leucovorin in human colorectal cancer cell lines. 262 28

To establish the effectiveness of adjuvant chemotherapy in patients with colon cancer after radical surgery, from 1980 to December 1983, 263 patients were randomized in a multicentric study to no further treatment (131 patients) or to a combination of fluorouracil (5-FU) (400 mg/m2 i.v., days 1-5) and lomustine (CCNU) (100 mg/m2 per os on day 5) every 6 weeks for 9 cycles (132 patients). The two groups were well balanced for age, sex, histology, tumor and nodal extent. Chemotherapy was not given to 30 of the 132 randomized patients, and of 98 treated patients only 38 completed the entire protocol. Analysis, as intention to treat, at 54 months did not show any significant difference between the two treatment groups in terms of relapse-free survival (surgery alone, 74.5%; surgery + adjuvant chemotherapy, 70.9%; p = 0.91). In contrast, a significant difference was observed in overall survival (surgery alone, 78.8%; surgery + adjuvant chemotherapy, 60.8%; p = 0.04). The sites of relapse were identical in the two treatment arms. In conclusion, from this study it appears that adjuvant chemotherapy with 5-FU and CCNU seems to have no efficacy in the cure rate of colon cancer patients.
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PMID:Adjuvant chemotherapy with fluorouracil and CCNU in colon cancer. Results of a multicentric randomized study. 267 80

While uncontrolled and retrospective studies suggest a treatment benefit for radiotherapy or chemotherapy when administered as adjuvant before or after surgical resection with a curative aim for colon cancer, prospective randomized clinicals trials failed to show any advantage and do not to date confirm the efficiency of the proposed adjuvant therapy. For rectal cancer, preoperative irradiation administered at the dose of 34.5 Gy and postoperative radiotherapy administered at the dose of 46 to 53 Gy markedly decreased the local recurrence rate, however, these treatments failed to improve the 5 year survival rate significantly. Recently the efficacy of a postoperative chemotherapy was observed in a randomized clinical trial. The administration of methyl-CCNU, Vincristine and 5-fluorouracil after surgical resection of rectal cancer improved both the disease-free survival and the survival rate. Another randomized study showed a benefit of combined post-operative radiotherapy and chemotherapy with methyl-CCNU and 5-FU. Advantages and disadvantages of preoperative irradiation treatment and postoperative irradiation treatment are discussed.
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PMID:Adjuvant therapy in colorectal cancer. 268 89

Fifty-seven patients with non-resectable liver metastases (31 from colon cancer, 26 from gastric cancer) received 5-FU, ADR, MMC combined hepatic arterial infusion therapy. (FAMia: 5-FU 334 mg/m2 qw, ADR 20 mg/m2 q4w, MMC 2.7 mg/m2 q2w; in colon cancer, 5-FU 167 mg/m2/day continuously for 3 months and then 334 mg/m2 qw). Myelo-suppression, hepatic arterial occlusion, gastroduodenal toxicity and elevation of biliary enzyme were observed at 29%, 39%, 32% and 13% in colon cancer, respectively, and at 35%, 8%, 0% and 0% in gastric cancer, respectively. Response rates evaluated by CT-scan were 63% (1 CR + 18 PR/30) in colon cancer and 79% (4 CR + 15 PR/24) in gastric cancer. Overall median survival was 352 days in colon cancer and 449 days in gastric cancer. Concerning background factors, the response rate in the well-differentiated type of colon cancer was significantly higher than in the moderately differentiated type, and significantly low in poorly differentiated medullary type gastric cancer. The existence of extra-hepatic lesions was the most important factor in survival in both cancers. [colon cancer: (-) 740 days vs (+) 267 days; gastric cancer: (-) 517 days vs (+) 245 days]. In conclusion, this therapy yields favorable direct effects on liver metastases from colon and gastric cancer without major side-effects and complications, but effective therapy of extrahepatic lesions is required for longer survival. Now, to release colon cancer patients from restrictions of continuous infusion pumps, a phase I study of weekly high dose 5-FU HAI therapy is under way.
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PMID:[A 5-FU, ADR, MMC combined hepatic arterial infusion therapy in non-resectable liver metastases from colon and gastric cancer]. 278 85

Fluorouracil (Adrucil) has been used for more than 20 years to treat metastatic colorectal carcinoma and has provided significant palliation of symptoms to some patients. Investigators are attempting to exploit pharmacologic aspects of fluorouracil that will provide further benefits. Prolonged infusion of the drug appears to overcome the problems of its brief half-life and the small percentage of cancer cells that are susceptible to the drug at any one time. The addition of leucovorin increases fluorouracil's ability to inhibit thymidylate synthase and thus colon cancer cell replication. It is hoped that the increased response rates produced by these advances will produce increased survival rates as well.
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PMID:Treatment of metastatic colorectal carcinoma. Recent advances in use of fluorouracil. 281 19


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