Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.
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PMID:A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy. 155 45

Based on promising results with 5-FU/FA or 5-FU/IFN-alpha in colorectal cancer, a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in patients with advanced pancreatic cancer. Patients received 9 million units (MU) IFN-alpha subcutaneously three times a week or 6 MU IFN-alpha once a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Fourteen patients, all previously untreated with chemotherapy, were enrolled; 13 (two females/11 males) were evaluable for response and toxicity (one too early). The median performance status was 80% (range, 60 to 100) and the median age 62 years. Besides the inoperable primary tumor, metastatic sites were liver, lung, and peritoneum. Three of 13 patients had a partial remission, three of 13 patients a minor response, and four of 13 patients no change. Three patients had progressive disease. Until now, no complete remission was seen. Median duration of response was 4+ months; median survival has not been reached yet. Of all patients there were three instances of World Health Organization grade 3 toxicity: fatigue (one of 13), nausea (one of 13), and diarrhea (one of 13); grade 4 toxicity did not occur. Although overall toxicity was moderate, most patients experienced a reduction of well-being. Therefore in all patients the dose of IFN was reduced (from 3 x 9 MU/week to 1 x 6 MU/week). Our preliminary data suggest that biochemical modulation of 5-FU with FA and IFN-alpha (reduced dosage) is effective in pancreatic cancer with moderate toxicity, warranting further study.
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PMID:Combination fluorouracil, folinic acid, and interferon alfa-2a: an active regimen in advanced pancreatic carcinoma. 155 50

Data are available on the principal side effects of individually administered biological response modifiers (BRMs). However, studies on physical symptoms secondary to multiagent regimens (i.e., combinations of BRMs and of BRMs and chemotherapy) are just now appearing in the literature. The combinations of alpha interferon and 5-FU and of alpha interferon and interleukin-2 (IL-2) are the focus of this paper. Published and unpublished reports of side effects associated with these combinations are reviewed, and resulting quality-of-life (QOL) issues examined. Physical side effects that may affect QOL are flu-like symptoms, gastrointestinal (GI) toxicities, and fatigue, which may alter social, physiological, and psychological function and negatively influence the perception of QOL. Nursing interventions to improve these reactions include awareness and assessment of the patient's perception of QOL and strategies to alleviate the symptoms. Numerous opportunities exist for nursing research on improved symptom management and on QOL in combination biotherapy regimens.
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PMID:Physical symptoms of combination biotherapy: a quality-of-life issue. 206 57

A resected case of a non-functioning adrenocortical tumor is reported. The patient's chief complaint was fever and general fatigue. Computed tomography and ultrasonography revealed the suspected presence of a tumor on the right lobe of the liver, though a definite diagnosis of a right adrenal tumor was reached after hepatic angiography. An endocrinal examination, however, showed no abnormality. The tumor was dissected sharply from the right hepatic lobe and completely removed with a part of the diaphragm. It measured 10 x 12 x 18 cm and weighed 1,280 g. Hemorrhagic and necrotic changes were noted in the cut section, and a subsequent pathological examination revealed an adenocarcinoma of the adrenal cortex. An administration of 5-FU was given orally and the patient's progress has gone well without a recurrence or a metastasis for 4 years and a month since the surgery.
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PMID:[A case of non-functioning adrenocortical tumor]. 235 70

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

Natural killer (NK) cell activity and psychological status were measured at baseline and at 3 months into treatment, as part of the National Cancer Institute (NCI) Protocol 79-C-111, randomizing breast cancer patients to lumpectomy/radiation v mastectomy. Patients who were found to have positive axillary lymph nodes also received combination chemotherapy (Adriamycin [Adria Laboratories, Columbus, OH], plus Cytoxan [Mead Johnson Pharmaceuticals, Evansville, IN] or methotrexate, plus 5-fluorouracil [5-FU]). Seventy-five patients were entered onto this behavioral immunology protocol at the time of data analysis. We reported in an earlier publication that NK activity was an important predictor of patient baseline prognosis relevant to nodal status. In that study, by using multiple regression analyses, 51% of the baseline NK activity variance could be accounted for by entering three distress indicators into the equation (patient "adjustment," lack of social support, and fatigue/depression symptoms). On reassessment of NK activity after 3 months, it was found that NK activity was not affected by the interim administration of chemotherapy and/or radiotherapy. However, consistent with our earlier findings, NK activity levels remained markedly lower in patients with positive nodes than in patients with negative nodes (at 60 to 1 effector to target cell [E:T] ratio, mean of 18% lytic activity v mean of 31% lytic activity [t = 1.87, P less than .05]). Even though average levels of NK activity were lower for patients with more tumor burden, there was still a substantial range of NK activity levels within the node positive patient group, as well as within the patient group as a whole. We hypothesized that differences in levels of NK activity could be predicted on the basis of baseline distress factors found to be significant in our earlier report. In fact, we found that we could account for 30% of NK activity level variance at 3 months follow-up on the basis of baseline NK activity, fatigue/depression, and lack of social support. Therefore, although neither radiation nor chemotherapy appeared to affect NK activity, tumor burden was again clearly associated with NK activity levels, and a significant amount of baseline and 3-month NK activity could be predicted on the basis of CNS-mediated effects. At the least, such factors provide a psychological marker of host biological status.
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PMID:Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer. 354 12

A 50-year-old woman with bilateral inflammatory breast cancer (T4, N1b, M1, Stage IV) underwent right extended radical mastectomy and left modified radical mastectomy following pre-operative administration of carcinostatics (ADM, 5-FU) and irradiation. However, tumor recurrence was observed at the skin and right pleural cavity after the operation. Adriamycin-containing combination chemotherapy and radiation therapy were performed, but no significant response was obtained. CDDP was then administered intravenously at a daily dose of 62.5 mg/m2 at intervals of 60 days. The pleural effusion disappeared and the extent of skin metastasis was reduced, resulting in partial response which lasted for 90 days. The serum CEA level decreased from 13.1 ng/ml to 2.3 ng/ml. As the side effects of this therapy, slight nausea, vomiting and general fatigue were observed. This result suggested that CDDP is an effective drug for inflammatory breast cancer.
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PMID:[A case report of inflammatory breast cancer effectively treated with cis-platinum]. 363 75

Clinical studies were prospectively conducted to quantitate the toxic side-effects of 5-FU administered by either the intravenous (i.v.) or intraperitoneal (i.p.) route. Sixty-six patients were treated following resection of a primary large bowel cancer after randomization to receive 5-FU by i.p. or i.v. routes. In both groups of patients, the dose of drug was increased a fixed amount until a toxic response occurred. At this point, the dose of drug was maintained or reduced in an attempt to complete 12 monthly treatment cycles of chemotherapy. The overall mean dose of drug administered by the i.p. route (1,479 mg) was significantly greater than given i.v. (1,019 mg), as it was for each treatment cycle. The primary adverse side-effect, resulting in drug dose stabilization or reduction, was leukocyte suppression of i.v. 5-FU or physical symptoms (abdominal pain or discomfort) for i.p. 5-FU (p2 = 0.0006 and p2 = 0.0318, respectively). The most frequent symptom reported by all patients was fatigue. Even though i.v. 5-FU dose was titrated to reduce toxicity, the nadir leukocyte count was suppressed over all cycles. The total numbers of immediate and delayed serious complications that resulted from i.v. or i.p. 5-FU were similar, although the nature of these complications differed markedly between the two routes of drug administration. Failure to complete 5-FU chemotherapy was significantly more common if patients received i.v. 5-FU plus pelvic irradiation. These studies indicate that intraperitoneal 5-FU administration decreases systemic drug effects even when the i.p. drug dose is increased to cause local toxicity.
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PMID:Toxicity studies of adjuvant intravenous versus intraperitoneal 5-FU in patients with advanced primary colon or rectal cancer. 377 3

A phase I study of weekly iv thymidine (TdR) and 5-FU was carried out in patients with advanced colorectal carcinoma using two dosage schedules. Schedule 1 employed a 3-hour infusion of TdR (6-8 g/m2/hour) followed immediately by a bolus of 5-FU (100-200 mg/m2). Schedule 2 used a slightly larger dose of TdR (18 g/m2/hour for 1.5 hours), with 5-FU given 30 minutes after the TdR infusion was started. Myelosuppression was observed erratically at the higher doses of 5-FU. Diarrhea and severe fatigue were seen frequently with Schedule 1. CNS side effects were the dose-limiting effects for both schedules. For long-term use the maximally tolerated 5-FU doses were 100 mg/m2/week for Schedule 1 and 175 mg/m2/week for Schedule 2. In pharmacokinetic studies in five patients, both schedules produced prolonged plasma beta-half-lives of 5-FU (96-189 minutes). Extensive formation of floxuridine was seen with both schedules. It appears likely that CNS toxic effects are characteristic of TdR-containing 5-FU regimens and would limit the therapeutic potential of this approach.
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PMID:Phase I evaluation and pharmacokinetic study of weekly iv thymidine and 5-FU in patients with advanced colorectal carcinoma. 397 91


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