Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011991 (diarrhea)
 57,543 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

"BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. The authors attempted to irradiate 3-5 days after the BUdR and antimetabolite had been infused via the superficial temporal artery, in 12 malignant oral tumours (11 squamous cell carcinomas and 1 reticulum-cell sarcoma). BUdR 50-250 mg/day, antimetabolites (5-FU) 10-250 mg/day and a total irradiation dose of 6000 rads by 6 MeV Linac X-ray or Co-60 gamma ray, 200 rads/day were given. 9 marked responses, 2 moderate responses and 1 no response (2 cases were operated on by local resection) were obtained by the authors. Side effects of treatment were observed during the course of "BAR" therapy. Stomatitis was found in all patients and it occurred on the mucosa of the tumour-affected site especially. Dermatitis of the skin of the face was noted in 6 cases, resembling irradiation dermatitis. Fever was observed in 4 cases and it always occurred after irradiation. Diarrhoea was noted in 3 cases and occurred before irradiation, 2 out of 3 were given BUdR 0.1 g and the remaining one was given BUdR 1 g, and 5-FU lg. In addition, there were: 1 loss of appetite, 1 nausea and 1 exfoliation of nails.
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PMID:The effects of "BAR" therapy on oral malignant tumors. 35 11

The effects of a group of elemental diets on the gastrointestinal toxicity of 5-FU in the Sprague-Dawley rat were evaluated. Diarrhea, stomatitis, hypoalbuminemia, and early deaths were more frequent in the animals on elemental diets than in those consuming standard rat chow. Sepsis and hypoalbuminemia were directly related to the extent of protein hydrolysis of the particular elemental diet.
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PMID:The adverse effects of elemental diets on tolerance for 5-FU toxicity in the rat. 59 49

In a prospectively randomized study the effect of adjuvant chemotherapy with 5-FU on survival and recurrence was analyzed in 274 evaluable patients with colorectal carcinoma who either underwent a curative or a palliative resection. In the treatment group, chemotherapy consisted of the intravenous administration of 5-FU 12 mg/kg daily for four consecutive days, then 6 mg/kg/per day on alternate days to the point of toxicity or to a maximum of 5 doses, followed by 12 mg/kg/week for one year. Drug toxicity was rarely severe and consisted of nausea and vomiting, diarrhea, stomatitis, leukopenia, and thrombocytopenia in slightly more than half of all patients. There have been no drug-related deaths. Analysis of the survival curves and disease-free interval curves reveal some evidence of drug benefit in both the curative group of resections and the palliative group of resections. However, this benefit is not significant except in those treated to toxicity. The disease-free interval after curative resection is significantly longer in patients treated with 5-FU to the point of toxicity with a white blood count less than 4,000 cells/mm3. We conclude that a preliminary analysis of the Central Oncology Group data in this trial does not make a convincing case for the use of 5-FU as an adjuvant to the surgical treatment of colorectal carcinoma.
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PMID:Adjuvant chemotherapy with 5-fluorouracil after surgical resection of colorectal carcinoma (COG protocol 7041). A preliminary report. 83 81

This Phase I study was designed to build on the Gastrointestinal Tumor Study Group's experience with combined modality therapy in patients with pancreatic cancer. Thirteen patients with adenocarcinoma of the pancreas received weekly 5-fluorouracil by rapid intravenous infusion midway through a 2-h infusion of high dose leucovorin during external beam radiation therapy. Twelve patients received 100% of planned external beam radiation; treatment delays occurred in only three. Four patients received 100% of planned chemotherapy doses. Leukopenia and thrombocytopenia caused reduction of the number of chemotherapy doses given during radiation in six patients; diarrhea, severe nausea and vomiting, and wound abscess caused reduction in three patients. Ten patients were evaluable for response; two had complete responses, one had a partial response, and two had minor responses. In this small series baseline and post-treatment CA 19-9 levels predicted and correlated with response. We conclude that radiation and 5-FU modulated by leucovorin is a tolerable treatment regimen for carcinoma of the pancreas, with preliminary suggestion of activity, that warrants further Phase II testing.
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PMID:Radiation therapy and 5-fluorouracil modulated by leucovorin for adenocarcinoma of the pancreas. A phase I study. 128 17

Five studies presented at the 1992 ASCO meeting are analysed. Kligerman's study was designed to determine if pre-treatment with WR-2721 could protect normal tissues from the toxicities induced by radiation therapy (in 100 patients with advanced rectal cancer). This pre-treatment resulted in a 13% reduction of moderate and severe acute toxicity. No WR-2721 patient experienced moderate or severe late toxicities compared to five in the group without pre-treatment. The complete response rate was higher in the WR-2721 group and there was no major WR-2721 related toxicity. Minski studied the acute toxicity (during treatment and two weeks after) of combined pelvic radiation therapy, 5-FU and leucovorin when delivered pre-operatively (16 patients) versus post-operatively (25 patients) in patients with rectal cancer. The toxicity criteria were fatigue, diarrhea, tenesmus, bowel movements, dysuria and erythema. Grade 3+ toxicity was more important in the post-operative therapy group (48% versus 13%). Given this high incidence of grade 3+ toxicity future randomized trials should explore the pre-operative approach. The final report of the inter group study of 5-FU plus levamisole as adjuvant therapy for stage C colon cancer was made by Moertel. With a median follow-up time of 5.5 years, the 5-FU plus levamisole treatment has reduced the recurrence rate by 39%, the cancer related death rate by 32% and the overall death rate by 31%. Most of the recurrences occurred during the first two years. There was a decrease in the liver, great omentum, peritoneum and lung metastases, but there was no modification in loco-regional recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cancers of the colon and the rectum: news in 1992]. 133 19

5-Fluorouracil (5-FU) is still the mainstay of chemotherapy in patients with metastatic colorectal cancer. A prolonged infusion of 5-FU is more active than any other schedule of 5-FU used to date. Cisplatin does not improve treatment results compared with 5-FU alone and is not recommended outside clinical trials. Biomodulation of 5-FU is a major step forward in the treatment of colorectal cancer patients and as the standard chemotherapy for advanced colorectal cancer. Two schedules of folinic acid daily for 5-day (low and high doses) and weekly high dose in combination with daily or weekly 5-FU are the most widely used schedules. Although the response rates to either schedule are comparable, the profile of toxicity is different, being stomatitis for the daily schedule and diarrhea for the weekly schedule as the dose-limiting toxicity. Modulation of 5-FU by methotrexate is time dependent. An interval of 24 hours between methotrexate and 5-FU is necessary for effective modulation. Other modulators, like interferon and N-phosphonoactyl-L-aspartate (PALA), are promising treatment options currently under investigation in randomized trials. The data from phase II and III trials using modulation of 5-FU by folinic acid, PALA, or methotrexate, or using continuous infusion 5-FU indicate that all of these strategies are active. Randomized trials are currently underway to further investigate these therapeutic approaches and whether a specific modulation offers more therapeutic advantages.
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PMID:Chemotherapeutic strategies in metastatic colorectal cancer: an overview of current clinical trials. 137 4

From April 89 to October 90, 41 patients operated for a Dukes B or C colorectal cancer were randomized to receive 6 courses of adjuvant treatment with (A) 5-FU alone (440 mg/m2 IV bolus 5/21 days) or (B) folinic acid (200 mg/m2 IV bolus 5/21 days) preceding 5-FU (370 mg/m2 in short infusion 5/21 days). Ten patients received also one course of immediate post-operative continuous portal infusion (5-FU 500 mg/m2/day x 7 followed by a 2 hours infusion of mitomycin C 10 mg/m2). The portal treatment was well tolerated (1 case of GI tract disturbances, 1 catheter obstruction). The toxicity of adjuvant systemic treatment was evaluated on 232 courses (125 A, 107 B). Hematologic and skin toxicities, alopecia and nausea-vomiting were mild. The limiting toxicities (expressed as percentages of courses) were stomatitis (grades 2-3: 11.4% A; 22.6% B) and diarrhea (grades 3-4: 7.3% A; 14.2% B; one toxic death was to deplore in arm B from a grade 4 diarrhea). The pilot study has demonstrated the feasibility of the adjuvant treatment proposed; a multicentric randomized trial (expected accrual: 800 patients) has therefore been activated on 11.01.90; all patients will also receive levamisole while radio-therapy will be mandatory for rectal cancer.
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PMID:[Tolerance of adjuvant treatment combining postoperative intraportal chemotherapy and a systemic treatment based on 5-fluorouracil in colorectal carcinoma with a histologically poor prognosis]. 146 46

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) daily for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridine, a new fluoropyrimidine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64%), lung (35%), local recurrence (10%) and peritoneum (10%). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxifluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.
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PMID:Reversal of resistance to doxifluridine and fluorouracil in metastatic colorectal cancer: the role of high-dose folinic acid. 146 82

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.
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PMID:Continuous regional treatment with fluoropyrimidines for metastases from colorectal carcinomas: influence of modulation with leucovorin. 153 72

Patients with advanced colorectal cancer were randomized to receive either fluorouracil (5-FU) 370 mg/m2 IV days 1 to 5 followed by weekly applications of 5-FU 600 mg/m2 or the same doses of 5-FU preceded by folinic acid 200 mg/m2. Because of toxicity, the weekly 5-FU dose in the combination treatment schedule was reduced to 500 mg/m2 in the course of the study. As of November 1990, 135 patients entered the study; 71 have received combination therapy, and 64 monotherapy. Sixty-three and 59 patients, respectively, are included in the present interim analysis. The two groups are well matched for age, performance status, site of disease, number of metastatic sites, and biochemical parameters. Treatment results are evaluable in 118 patients. Thirty percent receiving combination treatment and 20% receiving monotherapy achieved a complete or partial remission. There is no survival time difference between the groups. However, time to progression is superior in the combination treatment group (median 26 weeks compared with 13 weeks). The main toxicity was diarrhea during the weekly therapy. This was especially true for patients receiving combination treatment before the reduction of 5-FU dosage. In contrast to only four of 56 patients with monotherapy, 14 of 39 with the combination treatment at the initial dosage had severe diarrhea with two treatment-related deaths in this latter group. By reduction of 5-FU dosage during the weekly therapy severe diarrhea could be clearly reduced with only one of 18 patients suffering from diarrhea of World Health Organization grade 3. Other toxicity was usually mild. In conclusion, a prolongation of time to progression could be achieved by combination treatment of folinic acid and 5-FU, which was well tolerated when the weekly dose of 5-FU did not exceed 500 mg/m2.
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PMID:Fluorouracil versus folinic acid/fluorouracil in advanced colorectal cancer--preliminary results of a randomized trial. 155 40


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