Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leucovorin (LV), given intravenously the orally becomes 5, 10-methylene tetrahydrofolate in both cancer and normal cells. FdUMP which is an active metabolite of 5-FU binds tightly to thymidylate synthase in the presence of the cofactor 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Clinically, the combination of LV and 5-FU is given parenterally by two schedules; 5 consecutive days schedule and weekly schedule. Five 5 consecutive days-schedule is divided into 2 methods. One is a 200 mg/m2/day of LV by Machover, and the other is 20 mg/m2/day of LV by O'Connell. The weekly schedule is a 2-hour infusion of dl-LV (500 mg/m2) and iv bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion by Petrelli. A multicenter cooperative study in Japan was conducted to evaluate the clinical efficacy of LV and 5-FU using the weekly schedule by Petrelli. Response rates were 31.5% and 41.2% against advanced gastric and colorectal cancer respectively. Then, we carried out a randomized early phase II study using 250 mg/m2 of l-LV weekly (similar to the schedule of Petrelli's, armA) and 100 mg/m2 (similar to the schedule of Machover's, arm B) or 10 mg/m2 (similar to the schedule of O'Connell's, arm C) of l-LV for 5 consecutive days against gastric cancer. The response rate was 33.3% in arm A, 24.1% in arm B and no response in arm C. Toxicity was within acceptable limits, Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high-dose LV and 5-FU seems to be a very promising combination but, there was no responder using low dose (10 mg/m2) of l-LV schedule against gastric cancer patients.
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PMID:[High-dose leucovorin and 5-FU]. 162 51

In recent years the concept of metabolic modulation of fluoropyrimidines by leucovorin has been introduced clinically in patients with advanced colorectal cancer, breast cancer, gastric cancer and head and neck cancer among others. The concept of metabolic modulation was developed in the laboratory and employed clinically. Leucovorin is a noncytotoxic compound used to increase the therapeutic efficacy of 5-fluorouracil. Following 5-fluorouracil activation to 5-fluorodeoxyuridine monophosphates, its binding to thymidylate synthase is stabilized by the active cofactor, 5,10 methylene tetrahydrofolate and its polyglutamate forms. Under these conditions, both the extent and duration of inhibition of thymidylate synthase and consequently, DNA synthesis are more pronounced. The results of clinical trials (phase II and III) indicate that the response rates to 5-fluorouracil/leucovorin modulation are significantly higher than that of fluorouridine alone.
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PMID:Modulation of fluoropyrimidines by leucovorin: rationale and status. 183 38

Though many previous reports suggest the clinical significance of adjuvant chemotherapy in gastric cancer, they are not always confirmed by the statistics. Treatment failures could be attributed to the minor benefit of chemotherapy for advanced cases, too much tumor burdens after surgery relative to the antitumor effect of chemotherapy, and statistically inadequate operation of clinical study. Improvement would be expected in the near future by carrying out a well designed control study with incorporation of new drugs such as CDDP or etoposide, or powerful regimen with MTX and 5 FU, or 5 FU and Leucovorin.
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PMID:[Issues of adjuvant chemotherapy in gastric cancer: its clinical significance]. 202 98

A multicenter cooperative study was conducted from June 1988 to July 1989 to evaluate the clinical efficacy of high-dose dl-Leucovorin (dl-LV) and 5-FU treatment in 61 cases of advanced gastric and colorectal cancer. The administration schedule was a 2-hour infusion of dl-LV (500 mg/m2) and an IV bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion. Patients (pts.) were treated q week x 6 then evaluated for response. Thirty one gastric cancer pts. were divided into two groups; nine pts. treated with 30 min. infusion of 5-FU, and the remaining 23 pts. treated with IV bolus. PR was obtained in 2/9 (22.2%) and in 7/22 (31.8%) of the first and second group, respectively. An overall response rate was 9/31 (29%). Thirty colorectal cancer pts. were divided the same: 13 pts. treated with 30 min. infusion of 5-FU and the remaining 17 pts. treated with IV bolus. PR was obtained in 2/13 (15.4%) and in 7/17 (41.2) of the first and second groups, respectively. An overall response rate was 9/30 (30%). Median survival time for the gastric cancer group was 9.4 months, and for the colorectal cancer group was 13.6 months. Toxicity was within acceptable limits. Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high dose LV and 5-FU seems to be a very promising combination and warrants a further investigation.
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PMID:[High-dose leucovorin and 5-fluorouracil in advanced gastric and colorectal cancer. High-Dose Leucovorin and 5-FU Study Group]. 226 Aug 72

Sequential low-dose Methotrexate.5FU therapy was conducted on a total 52 cases of advanced or recurrent gastric carcinoma. Intra-aortic infusion therapy was performed in 31 cases and intravenous administrative therapy was employed in the remaining 21 cases. The two groups were compared in terms of the response rate and side effects. Thirty mg/m2 of Methotrexate (MTX) was given by bolus injection into the aorta or venous route, followed by 500 mg or 750 mg of 5FU by bolus injection 3 hours later. Twenty four hours after the injection of MTX, 30 mg of Leucovorin was given intravenously or orally. The major lesion of intra-aortic infusion group was primary site (stomach) in 10 cases, peritoneum and digestive tract in 9 cases, Douglas' pouch in 5 cases, liver in 3 cases, abdominal wall in 2 cases and retro-peritoneal lymph nodes in 2 cases. On the other hand, the major lesion of the intravenous administrative group was the primary site (stomach) in 5 cases, peritoneum and digestive tract in 6 cases, Virchow's lymph-node in one, hepatic hilus in one and lung in one. Response could be evaluated in 31 patients with intra-aortic therapy. Partial response was found in 9 cases and NC in 16. PD was found in 5 and so the rate of response was 29.0% (9/31). The major lesion of 9 responders was inoperable Borrmann's Type 4 gastric cancer in 2 cases, peritoneal recurrence with an abdominal mass in 4, recurrence in the abdominal wall in one, Douglas' pouch in one, and intestinal stenosis in one.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Sequential methotrexate.5FU chemotherapy for gastric cancer--comparison between intra-aortic infusion therapy and intravenous administration therapy]. 235 57

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

A multicenter cooperative study was conducted from July 1984 to March 1986 to evaluate the clinical efficacy of sequential MTX-5-FU treatment in 96 cases of advanced gastric cancer and 39 cases of colorectal cancer. 5-FU 600 mg/m2 i.v. was given and MTX 30 mg/m2 (A), 100 mg/m2 (B) and 300 mg/m2 (C) i.v. were given, and the administration interval between MTX and 5-FU was 1 to 3 h for the gastric cancer group, and 7 h for the colorectal cancer group. Leucovorin rescue of 10 mg/m2 p.o. was given 24 h after MTX administration. In the gastric cancer group, the response rate for Regimen A was 23.2% (CR 1 and PR 12) out of 56 evaluable cases, and for Regimen B, 40.5% (CR 1 and PR 14) out of 37 evaluable cases. In the colorectal cancer group, the response rate for Regimen A was 28.6% (PR 6) out of 21 evaluable cases and for Regimen B, 20.0% (PR 3) out of 15 cases. Median survival time for the gastric cancer group was 5.5 months with Regimen A and 7.6 months with Regimen B, and for the colorectal cancer group 10.9 months with Regimen A and 7.9 months with Regimen B. Main adverse effects were marrow impairment and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In this study Regimen B showed relatively good results. In order to evaluate the biochemical modulation occurring with sequential MTX-5-FU treatment, a further phase III study in gastric cancer patients should be conducted.
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PMID:[Sequential methotrexate-5-fluorouracil (MTX-5-FU) treatment of patients with advanced gastric and colorectal cancer. Sequential Methotrexate-5-FU Study Group]. 361 60

Sequential MTX/5-FU therapy was performed on 64 patients with unresectable or recurrent gastric cancer. The therapy was most effective in patients with poorly differentiated type gastric cancer. We adopted the intermediate (MTX: 100mg/m2, 5-FU: 800mg/m2) and low (MTX: 30mg/m2, 5-FU: 600 mg/m2) dose regimens. The latter was performed at the outpatient clinic every 2 weeks. This therapy was used for patients with Borrmann type 4 gastric cancer or advanced gastric cancer of poorly differentiated type as postoperative adjuvant chemotherapy. The response rate was 25% in 44 evaluable patients, and 33% in patients with poorly differentiated type cancer. As an adverse effect, leukopenia (grade 3, 4) was observed in 4 patients (9%). The 5-year cumulative survival rate of the sequential MTX/5-FU therapy group (52.6%) was much better than the conventional adjuvant chemotherapy group (32.1%) in patients who underwent curative resection with Borrmann type 4 gastric cancer. One patient survived more than 900 days after non-curative resection with peritoneal dissemination (P 3) after low dose therapy of sequential MTX/5-FU. For the patients who did not respond to the MTX/5-FU therapy, MTX/CDDP/LV/5-FU therapy was adopted. This protocol consisted of MTX (30 mg/m2 iv; day 1), CDDP (60 mg/m2 div; day 2 and day 9), Leucovorin (30 mg iv; day 2-9) and 5-FU (250 mg/m2 div; day 2-9). We also performed MTX/CDDP/LV/5-FU therapy for the treatment of differentiated type gastric cancer.
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PMID:[Clinical evaluation of sequential MTX/5-FU therapy for gastric cancer]. 761 69

Recurrence of gastric cancer or colon cancer was observed in some patients who received 5-fluorouracil (5-FU) high-dose continuous Methotrexate (MTX)-Leucovorin (LV) therapy (FML therapy) previously. 5-FU high-dose 48-hours continuous therapy (5-FU therapy) as maintenance therapy for the patients was performed in the hospital and successively at home. The patients included 3 with recurrent gastric cancer and 2 with recurrent colon cancer: there were 4 males and 1 female, the mean age was 51.8 years (33-59 years). All patients had received FML therapy during the hospital stay before the maintenance chemotherapy at home. 5-FU therapy (30 mg/kg/day x 2 days/w), 30.2 courses on an average (11-40 courses), was performed through a catheter (Port-A-Cath), which was introduced into the right subclavian vein and placed under the skin, with a Baxter infusion pump. The concentration of 5-FU was 197 +/- 172-401 +/- 127 ng/ml between the 2nd and 48th hour. Adverse reaction included anorexia in 5 patients, stomatitis in 4, pigmentation in 4, leukopenia in 3, neuropathy in 2 and alopecia in 1. The therapy was effective for 10.4 months on an average (4-18 months) and the mean survival period was 12.0 months (7-18 months).
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PMID:[Usefulness of 5-FU high-dose continuous therapy at home in patients with recurrent gastric and colon cancer]. 780 45

Eleven patients with chemotherapeutically pretreated advanced gastric cancer were treated in a phase II study with a combination of 5-fluorouracil (5-FU) and Leucovorin (LV, folinic acid). 5-FU (1,200 mg/m2) and LV (100 mg/m2) were given as a parallel continuous intravenous infusion over 48 h every 2 weeks for at least 8 weeks. Toxicity and response rates were evaluated. Results show that this chemotherapeutic regimen is well tolerable, without any side effects exceeding WHO grade 1 toxicity, but that it has no considerable effects on tumor growth. None of the patients achieved disease remission. In 8 out of the 11 study patients therapy had to be discontinued prematurely because of disease progression. Therefore we conclude that the studied protocol of 5-FU/LV as second-line treatment of advanced gastric cancer although well tolerable is not effective.
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PMID:Continuous 5-fluorouracil and leucovorin as a second-line therapy for advanced gastric carcinoma. 797 Apr 94


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