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)

A multicenter, phase II trial of continuous-infusion interleukin 2 (IL-2) was done in the Southwest Oncology Group to evaluate the efficacy and safety of this treatment in a broad-based population of patients with metastatic renal-cell carcinoma. Forty-seven patients from 11 different institutions were entered in this study, with 43 eligible. Two technically ineligible patients who received treatment and for whom records are available are included in the data analysis. Thus, there are 45 analyzable patients. Of these patients, performance status was 0 in 58% and 1 in 42%. Thirty-one patients had a prior nephrectomy, and 12 patients had received prior therapy. IL-2 was initially given at a dose of 4.5 x 10(6) Roche U/m2/day, 4 days a week, for 4 weeks in a row, followed by a 3-week rest period. Because of the difficulty in obtaining reimbursement for the hospitalization required on the days of IL-2 administration, after 10 patients had been entered, the treatment regimen was changed to 6 x 10(6) Roche U/m2/day for 4 days as an inpatient, followed by 2 weeks of potential outpatient treatment at a dose of 3 x 10(6) Roche U/m2/day for 4 days each week. This was followed by a 2-week rest period. Within the 45 analyzable patients, there were 0 complete responses and 6 partial responses, for a response rate of 13% (95% confidence interval 5.1-27%). Responses occurred in lung metastases, nodal disease, and in one patient with bone metastases and the primary kidney tumor. Response durations were 1 month, 1 month, 14+ months, 19 months, 26+ months, and 27 months. Of 12 patients with a nephrectomy and only lung metastases, 4 showed partial responses. Medial survival for all analyzable patients is 15 months (95% confidence interval 8-20 months). Toxicity was significant, with nausea and vomiting, diarrhea, fever and chills, dermatologic changes, and fatigue the most frequent. There were 18 instances of grade 4 toxicity, with the most common grade 4 toxicity, respiratory, found in 8 patients. There were two early deaths of probable heart-related causes while receiving treatment. A continuous-infusion IL-2 regimen that allows some potential outpatient treatment shows effectiveness and toxicity similar to that in other multicenter IL-2 infusion trials and high-dose intravenous bolus regimens.
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PMID:A phase II trial of continuous-infusion recombinant interleukin-2 in patients with advanced renal cell carcinoma: a Southwest Oncology Group study. 857 65

We report on the clinical course of 15 patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant beta-interferon as part of a phase I-II study. There were no objective responders among the 15 patients treated with recombinant beta-interferon at an i.v. dose escalating from 90 X 10(6) U given three times a week until there was documented disease progression or complete response (CR). Overall median survival was 24 months. One patient refused further treatment after 7 weeks. The major side effects of treatment included cardiovascular events (20%), mental status change requiring cessation of drug (6.7%), and grade 3 headaches/myalgias (26.7%). There were no life-threatening side effects observed; however, cardiac events led to the termination of treatment in three patients. Other minor toxicities included fatigue (46.7%), proteinuria (60%), diarrhea (6.7%), nausea and vomiting (13.3%), persistent fever (6.7%) and transient visual disturbance (6.7%). Thus, at our institution, in a cohort of 15 patients with metastatic RCC, recombinant beta-interferon when given i.V. at a dose < or equal to 720 X 10(6) U three times per week, yielded no clinical antitumor activity. A review of the literature on the use of beta-interferon for metastatic RCC suggests that there may be some efficacy, but our experience with escalating i.v. doses < or equal to 720 X 10(6) U given three times a week does not support it. Moreover, at these doses, one may find serious cardiovascular events although further studies need to be done in order to clearly define dose-related side effects as well as optimal efficacy-to-toxicity ratio.
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PMID:Recombinant beta-interferon in the treatment of patients with metastatic renal cell carcinoma. 861 Jun 47

CPT-11 (irinotecan) is a promising anticancer agent with a novel mechanism of action dependent on the inhibition of the DNA eukaryotic enzyme, topoisomerase I. The clinical utility of CPT-11 in advanced colorectal cancer has been documented in more than 400 patients recruited in phase II clinical trials in Europe, Japan, and United States. Among 178 eligible patients in a multicenter European study, the overall response rate to CPT-11 on a once-every-3-weeks regimen was 18%, and the median duration of response was 9.1 months. Thirty-two percent of the patients had no evidence of disease progression at 6 months. These results were similar in chemotherapy-naive and pretreated patients. These findings are consistent with the results of other studies conducted in Japan and the United States in which a weekly CPT-11 regimen was associated with response rates of 15% to 32% in chemotherapy-naive or pretreated patients. The principal adverse events of CPT-11 are neutropenia and delayed diarrhea, which in the European studies developed as grade 3 or 4 toxicity in 21% and 12% of the cycles (47% and 38% of patients), respectively. Neutropenia did not appear to be cumulative, with total recovery by day 22 in most cases. Loperamide was considered the most effective agent for controlling delayed diarrhea. Other adverse events included an early cholinergic-like syndrome (consisting of diaphoresis, early diarrhea, and abdominal cramps), nausea and vomiting, fatigue, and alopecia. In conclusion, CPT-11 has shown promising antitumor activity in the treatment of patients with advanced colorectal cancer, including those refractory to 5-fluorouracil (5-FU)-based regimens, suggesting no cross-resistance to 5-FU. CPT-11 appears to have activity similar to that of 5-FU in first-line treatment and, moreover, remains active after failure of 5-FU therapy. The specific gastrointestinal toxicity is manageable, and a better control of this type of toxicity is expected in the future. CPT-11 would therefore appear a welcome addition to the oncology armamentarium for this difficult-to-treat malignancy.
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PMID:CPT-11 in the treatment of colorectal cancer: clinical efficacy and safety profile. 863 52

CI-973 is a water-soluble platinum diamine complex whose antitumor activity is greater than that of cisplatin in some murine tumors. It has shown activity against cisplatin-resistant tumors. This phase II trial had the objectives of determining the therapeutic efficacy of CI-973 in patients with metastatic breast cancer who had been treated with one prior chemotherapy regimen, and of further defining the toxicity of the agent and the reversibility of its toxicity. CI-973 was administered as an intravenous infusion over 30 min with no prehydration or antiemetic programs. Treatment cycles were repeated at 21-day intervals. Patients with histologically confirmed metastatic breast cancer, measurable disease, and good performance status who had received only one prior chemotherapy regimen for metastatic disease were eligible for treatment. Adequate hematologic, renal, and hepatic function were required. A total of 26 patients received a median of two courses of CI-973 (range, 1-18 courses). Hematologic toxicity was severe: nearly all patients experienced granulocytopenia with granulocyte counts of 0 at all dose levels. Nevertheless, neutropenic fever and documented systemic infection were uncommon, and there were no hospitalizations for neutropenic fever or infection. Visceral disease dominated in this patient group. Of the 26 patients, 14 had visceral disease, 6 had bone or bone marrow disease, and 6 had skin, soft-tissue, or lymph-node disease. Of the 26 patients treated, 25 were evaluable for response. There were two partial remissions, one in liver and one in bone, and three minor responses, for a response rate of 8%. Nonhematologic toxic effects were mild and consisted of nausea and vomiting, fatigue, minimum peripheral paresthesia, and hypomagnesemia. Further study of CI-973 at the dose and schedule used in this study is not warranted. Because this agent had no significant extramedullary toxicity, intensification of the dose of CI-973 with concomitant administration of colony-stimulating factors has the potential to improve response in this patient population.
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PMID:A phase II study of CI-973 [SP-4-3(R)]-1,1-cyclobutane-dicarboxylato (2-)] (2-methyl-1,4-butanediamine-N, N') platinum in patients with refractory advanced breast cancer. 864 5

Malnutrition, which is common in maintenance dialysis patients, is strongly associated with increased morbidity and mortality. An important contributing factor is anorexia, leading to reduced intake in relation to the recommended allowances, which for protein is higher than in healthy subjects. Uremic toxicity in underdialyzed patients may cause anorexia as a result of retention of toxic compounds in the middle molecular weight range, which are normally excreted in the urine. Various comorbidity factors and psychosocial and economic factors may also be associated with low nutritional intake. The hemodialysis procedure may reduce nutritional intake because of cardiovascular instability with nausea and vomiting and post-dialysis fatigue. Abdominal discomfort, absorption of glucose and amino acids, and peritonitis may reduce appetite in peritoneal dialysis patients. Underdialysis, if present, should be corrected and various catabolic factors such as acidosis, infections, and other comorbidity factors should be treated, dietary counseling should be given, and psychosocial and economic support should be provided when needed. Patients who remain malnourished despite such measures may be given parenteral or enteral nutritional supplementation. Peritoneal dialysis solutions with amino acids have been used successfully in CAPD patients who suffer from protein malnutrition. Recombinant human growth hormone and IGF-1 are new treatment alternatives that need further evaluation.
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PMID:Anorexia in dialysis patients. 873 65

During December 1993-September 1995, the Bureau of Food and Drug Safety, Texas Department of Health (TDH), received approximately 500 reports of adverse events in persons who consumed dietary supplement products containing ephedrine and associated alkaloids (pseudoephedrine, norephedrine, and N-methyl ephedrine). This total included reports by individuals and reports identified by the Bureau of Epidemiology, TDH, in a review of records from the six centers of the Texas Poison Center Network. Reported adverse events ranged in severity from tremor and headache to death in eight ephedrine users and included reports of stroke, myocardial infarction, chest pain, seizures, insomnia, nausea and vomiting, fatigue, and dizziness. Seven of the eight reported fatalities were attributed to myocardial infarction or cerebrovascular accident. This report describes three patients in which the recommended dosage for the dietary supplements reportedly was not exceeded, summarizes results from ongoing investigations, and underscores the potential health risks associated with the use of products containing ephedrine.
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PMID:Adverse events associated with ephedrine-containing products--Texas, December 1993-September 1995. 877 3

A combination chemotherapy (PT treatment) with cisplatin and tetrahydropyranyl-adriamycin (THP-ADM) was performed in 17 patients with head and neck squamous cell carcinoma. Chemotherapy treatment began with an intravenous dose of 50 mg/body cisplatin and an intravenous dose of 20 mg/body THP-ADM. Administration of THP-adriamycin was performed on the first day only, while cisplatin treatment was repeated once a day until the third day. Five of the 17 cases achieved complete response (29.4%) and seven achieved partial response. Response rate was 70.6%. Toxicity was mild and controlled with symptomatic treatment. Leukopenia was observed in 71.4% thrombocytopenia 14.3% (due to myelosuppression), appetite loss 38.1%, general fatigue 28.6% and nausea and vomiting 23.8%. No electrocardiographic abnormality was noted.
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PMID:Combined chemotherapy and radiation therapy in head and neck cancer. 879 Jul 67

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM. From January 1988 until April 1994, 88 patients with recurrent or metastatic AGC were randomly received 5FU, EPI, MMC with (group A) or without (group B) LV. Between the two arms of the study no difference was noticed in sex, performance status, primary site of tumor, and lymph node metastases. Therapy included group A (5FU 600 mg/m2/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m2/day, i.v. bolus, on days 1 and 29, MMC 10 mg/m2/day, i.v. bolus, on day 1) and group B (the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there were two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significantly higher number of patients achieving stable disease was observed in group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). There were more patients with progressive disease in group A 25 (59%) than in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted in mean duration of response: group A, 15.8 (6-31) weeks; and group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients from disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not evaluable because they abandoned therapy after the first cycle. Toxicity was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically different when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate was increased in the schedule with the addition of LV, at the cost of increased toxicity and with no difference in survival. A randomized trial comparing FEM-LV with new generation regimens would determine whether the addition of LV qualifies FAM equally active with these.
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PMID:5-Fluorouracil, epirubicin, and mitomycin C versus 5-fluorouracil, epirubicin, mitomycin C, and leucovorin in advanced gastric carcinoma. A randomized trial. 882 83

Thirty-six patients with advanced epithelial ovarian cancer received epirubicin as second-line therapy after primary treatment with carboplatin and cyclophosphamide. Thirty-four patients were evaluatable for response, 36 for toxicity. There were 9 responses (response rate 26.4%, 95% CI = 12.9-44.4), 2 complete and 7 partial. Median duration of response was 149 days (range 42-183); 4 patients with partial remission are still on study. Toxicity consisted of fatal cardiac failure and paravenous injection (1 patient), fatal leukopenia and sepsis (1 patient), and severe loss of appetite, nausea and vomiting, fatigue, and general malaise in 3 patients. Platelet nadir grade 4 (WHO) was observed in 2 patients while leukocyte nadir grade 4 was seen in 3 patients. The present study showed a high response rate from standard-dose epirubicin. Toxicity was acceptable in most patients, but 2 patients died from treatment complications which gives a treatment-related mortality rate of 6%. Response was primarily seen in patients with minor tumor load and in good general condition.
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PMID:A phase 2 study with epirubicin as second-line treatment of patients with advanced epithelial ovarian cancer. 891 Jun 29

Given their known activity against non-small cell lung cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin were combined in this phase I study of patients with metastatic disease to determine the maximum tolerated dose and the dose-limiting toxicity of the combination. The initial dose of paclitaxel was fixed at 135 mg/m2 given as a 24-hour infusion with carboplatin administered in escalating doses in cohorts using Calvert's formula-dose (mg) = target AUC x (GFR + 25), where AUC is area under the concentration-time curve and GFR is glomerular filtration rate-based on target AUCs of 5, 7, 9, or 11 mg/mL.min. Dose escalations were based on cycle 1 toxicities. Filgrastim was not administered with the first cycle until two or more patients developed grade 4 or febrile neutropenia at the preceding dose level. Dose-limiting toxicity occurred in two patients at level 2 (cycle 1), and filgrastim was administered thereafter for the next four dose levels. Grade 4 thrombocytopenia was seen at level 4; thus, the carboplatin dose was de-escalated thereafter, and the paclitaxel dose escalated. Rare nonhematologic toxicities include fatigue, diarrhea, and nausea and vomiting. Among the first 30 patients, one had a complete response and 14 had partial responses, for an overall response rate of 50%. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II dose without filgrastim support is paclitaxel 175 mg/m2 via a 24-hour infusion with the carboplatin dose targeted to achieve an AUC of 7 mg/ mL.min.
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PMID:Paclitaxel and carboplatin in metastatic non-small cell lung cancer: preliminary results of a phase I study. 894 6


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