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

A phase II study on recombinant human leukocyte A interferon (rIFN-alpha A) was carried out in 30 patients with urogenital cancers. Each patient received rIFN-alpha A by i.m. injection every day for at least 4 weeks. The initial daily dose was 3 X 10(6) U, being escalated at intervals of 3 days or more up to 50 X 10(6) U. The results are summarized as follows: In aged patients, the daily dose appropriate for everyday i.m. injection was considered to be 9 X 10(6) U or below, judging from the adverse reactions observed. According to Koyama and Saito's response criteria, partial response (PR) and minor response (MR) were obtained, respectively, in 3 and 1 out of 12 patients with renal cell carcinoma, while PR was seen in 1 out of 9 with urothelial cancer. No response was observed in patients with testicular cancer and in those with prostatic cancer. Various kinds of adverse reactions were recognized and each patient showed one reaction or more. Fever, fatigue, leukopenia, anemia, thrombocytopenia and elevation of GOT and GPT were observed relatively frequently. Among these, fatigue and thrombocytopenia were regarded as dose limiting factors.
 ...
PMID:[Phase II study of recombinant human leukocyte A interferon on urogenital cancer patients]. 400 82

It is unclear from preliminary laboratory studies whether a high- or a low-dose interferon treatment strategy is optimal. As part of an ongoing study of mechanisms of interferon action, we have evaluated toxicity in a two-arm protocol in which patients were randomly assigned to receive lymphoblastoid interferon by either a low-dose treatment strategy (2 X 10(6) units/m2 daily X 28 days then daily X 5 days every other week by im injection) or a high-dose treatment strategy (5 X 10(6) units/m2 by continuous iv infusion over 24 hours, escalating by 5 X 10(6) units/m2/day as tolerated over 10 days, repeated every 28 days). The main toxic effects in both arms were fever, fatigue, and anorexia. Marked interpatient differences within each dose arm were greater than differences between arms. Additional significant toxic effects included nausea and vomiting, hypotension, leukopenia, thrombocytopenia, and evidence of hepatic toxicity. Minor changes in serum electrolytes were noted. Coagulation studies were normal. The dose-limiting toxic effect for the high-dose arm was myelosuppression. Median maximum tolerated dose among high-dose strategy patients was 18 X 10(6) units/m2, but there was marked interpatient variation. We conclude that both dose schedules were relatively well-tolerated. Because of individual variation in tolerance, high-dose treatment should include a dose escalation strategy.
 ...
PMID:Prospectively randomized toxicity study of high-dose versus low-dose treatment strategies for lymphoblastoid interferon. 401 85

Thirty-five eligible patients with disseminated malignant melanoma received intramuscular recombinant leukocyte interferon (IFN-rA), 50 X 10(6) U/m2 three times weekly (TIW) for an intended duration of 12 weeks concomitant with daily oral cimetidine, 1,200 mg/d in four divided doses. For all study participants, the median survival time was six months. Among 21 "good risk" patients (performance score [PS] 0, 1 and no prior chemotherapy), we observed seven partial regressions (33%). Six patients had stability of disease (29%), seven had immediate disease progression, and one discontinued treatment after two doses without tumor evaluation due to side effects. Times to disease progression of five patients with regressions of soft-tissue disease were 2.1, 3.3, 3.5, 3.7, and 4.3 months. Two patients had partial regressions of lung nodules for 2.0 and 3.8 months. We observed one regression among 14 "poor risk" patients (PS 2, 3, or prior chemotherapy). A 46-year-old woman with prior treatment had a partial regression of soft-tissue disease for 4.1 months. Four "poor risk" patients achieved disease stability, and nine progressed immediately. Leukopenia (WBC count less than 4,100/microL) affected 21 (66%) of 32 patients with WBC count data. The median count was 3,100/microL; range, 1,300 to 8,400/microL. We detected two cases of mild thrombocytopenia (100,000 and 120,000/microL). Other noteworthy toxicities included moderate-to-severe nausea (34%), anorexia (63%), and fatigue (80%). All patients experienced myalgias. Twenty patients had dosage decreases during the first cycle, and 14 of the 16 patients remaining on study after the first cycle required dosage reductions. The overall response rate is similar to our prior studies with IFN-rA as a single agent using TIW doses of 50 X 10(6) U/m2 and 12 X 10(6) U/m2 among 31 and 30 patients, respectively.
 ...
PMID:Phase II study of recombinant leukocyte A interferon (IFN-rA) plus cimetidine in disseminated malignant melanoma. 402 Apr 8

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.
 ...
PMID:Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report. 402 Apr 10

The purpose of this study was to evaluate the toxicity and antitumor activity of low doses of human lymphoblastoid interferon in 36 patients with measurable disease in whom higher priority treatment methods had failed. All but one had surgically confirmed advanced disease and had undergone initial treatment with a multiagent chemotherapeutic regimen in combination with cisplatin; four patients had also received radiation therapy. Their age range was 28 to 74 years. All had Gynecologic Oncology Group performance grade 2 or better (Karnofsky, 50% and above). Human lymphoblastoid interferon was administered at 5 megaunits/m2 intramuscularly, for 5 days per week (Monday through Friday) for 6 consecutive weeks. Patients who exhibited response or stable disease at 6 weeks were placed on a regimen of maintenance therapy at the same dose level for 2 days per week (Monday and Tuesday), for up to 12 months or until progression. Twenty-eight patients were evaluable for response: two with complete responses (7.1%), three with partial responses (10.8%), 14 with stable disease (50.0%), and nine with increasing disease (32.0%). Among the cumulative adverse effects, fatigue was most common, followed by moderate leukopenia and thrombocytopenia. Other observed adverse effects consisted of severe nephrotoxicity in two patients and myocardial infarction in one patient. It appears that therapy with human lymphoblastoid interferon may have cytostatic and possibly cytotoxic effects in this group of patients, with acceptable adverse reactions.
 ...
PMID:Human lymphoblastoid interferon in the treatment of advanced epithelial ovarian malignancies: a Gynecologic Oncology Group Study. 404 Mar 29

Sixteen patients with advanced cancer were treated with recombinant-DNA-produced pure leukocyte A interferon (IFLrA) intramuscularly in doses ranging from 3 to 198 X 10(6) units. with interval periods of 72 to 96 hours between doses. At the two lowest doses of 3 and 9 million units, there was a cross-over evaluation between IFLrA and partially pure leukocyte interferon (IFN-C) produced from human cells. THe maximum observed serum concentration of IFLrA measured by enzyme immunoassay and bioassay increased with increasing doses. The mean serum concentrations of IFLrA and IFN-C were similar. Clinical effects produced by IFLrA and IFN-C were similar, including fever, chills, myalgias, headache fatigue, and reversible leukopenia and granulocytopenia. Eight patients had transient and mild numbness of the hands or feet, or both. Three patients developed low titers of antibody to IFLrA, Seven of 16 patients showed objective evidence of tumor regression during the study.
 ...
PMID:Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. 617 59

A multi-institutional trials program was initiated to define the effects of interferons in disseminated human breast carcinoma. Interferon alpha, prepared from buffy coats, was administered intramuscularly at 3 x 10(6) U daily for an initial period of 28 days. Of 23 patients who entered the program, five had an objective partial response of 92 days mean duration at diverse sites of involvement. Patients who responded were significantly older (p = 0.05) than nonresponders. Dose escalation in eight patients did not result in any clear evidence of additional responses. Major toxicities were fatigue, anorexia with weight loss, and reversible leukopenia (less than 3.5 x 10(9) leukocytes/L in 16 patients). Natural killer cell and antibody-dependent cell-mediated cytotoxicity were significantly (p less than 0.05) enhanced 48 hours after interferon administration began but subsequently declined despite continued therapy. Serum beta 2-microglobulin concentration increased on day 15 (p less than 0.05) and remained significantly elevated on day 22 (p less than 0.005). Peak interferon titers (mean, 62 U) occurred 6 hours after interferon was started, varied widely between patients, and were higher and more persistent with dose escalation. Once an optimal dose is defined, prospectively randomized trials will define what role interferons may have in systemic therapy of breast carcinoma.
 ...
PMID:Leukocyte-derived interferon (alpha) in human breast carcinoma. The American Cancer Society phase II trial. 617 35

6 patients with amyotrophic lateral sclerosis were treated with intravenous infusion of 100-200 million IU per day of human leukocyte interferon. Side effects of treatment included fever, chills, malaise, nausea, marked leukopenia, mild anemia, and thrombocytopenia. Tiredness, confusion, papilledema, and overall signs of acute encephalitis were observed. Tendon reflexes and muscle force decreased. EEG activity was slowed, and evoked potentials showed significant slowing of conduction times. Neuropsychological tests revealed congitive dysfunction. The syndrome of inappropriate antidiuretic hormone secretion developed in all patients. All side effects were reversible with cessation of interferon treatment.
 ...
PMID:Neurotoxic and other side effects of high-dose interferon in amyotrophic lateral sclerosis. 620 81

A cooperative phase I-II study of HLBI (human lymphoblastoid interferon), natural interferon-alpha, was carried out in 38 major institutions in Japan. The eligibility of patients and evaluation of tumor response were based on the 'Criteria for the Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumor' by Koyama and Saito, and on Blood Cancer by Kimura. Major objectives of the phase I study were pharmacokinetics and toxicity of HLBI . Based on the toxicity observed in 5 patients with advanced breast cancer, the maximum tolerated dose (MTD) was determined to be 12 X 10(6) unit/day for 1 month. In phase II study, HLBI was administered by i.m. injection at a dose of 3-6 X 10(6) unit/day. Out of 391 patients entered into this study, 280 patients were evaluable. Complete and partial responses were observed in 40 (14.3%) out of 280 evaluable patients, including 11 (19.6%) out of 56 renal cell cancers, 14 (19.2%) out of 73 multiple myelomas, and 9 (17.3%) out of 52 malignant lymphomas among others. Major side effects were fever (69.8%), gastrointestinal disturbances (31.4%), leukopenia (30.7%), thrombocytopenia (27.8%), hepatotoxicities (23.6%) and general fatigue (22.1%).
 ...
PMID:[A cooperative phase I-II study of HLBI in patients with malignant tumors]. 632 4

Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule.
 ...
PMID:Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial. 634 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>