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)

Twenty-nine patients with recurrent or advanced, incurable head and neck cancer were entered into a phase I-II trial of carboplatin in combination with 5-fluorouracil (5-FU), 1,000 mg/m2/d continuous intravenous (IV) infusion for five days every 28 days. The initial dose of carboplatin was 300 mg/m2 for patients with Karnofsky performance scores greater than or equal to 70%, and 240 mg/m2 for patients with scores of 50% to 60%. Subsequent doses were modified to achieve grade 2 myelo-suppression: WBC, 2,000 to 2,999 cells/microL; granulocytes, 1,000 to 1,499 cells/microL; and platelets, 50,000 to 75,000 cells/microL. Dose levels were 180, 240, 300, 360, and 420 mg/m2. Twenty-eight patients had squamous-cell cancers and one had an adenoid cystic carcinoma of the parotid. There were 26 patients with recurrent disease; 22 had received prior RT; only two had received other chemotherapy immediately before study entry. Three patients had newly diagnosed incurable stage IV disease. The median performance status was 80% (range, 60% to 90%). All patients had objectively measurable disease, and 28 were evaluable for response. There were three complete responses (CRs) and ten partial responses (PRs) (48% CR and PR); the median duration of response was 4.7 months (range, 1.5 to 15+ months). Dose-limiting toxicities were granulocytopenia, thrombocytopenia, and stomatitis. Prolonged myelosuppression delayed retreatment in eight patients and delayed 19 of 107 (18%) courses. Stomatitis occurred in 61% and diarrhea in 29%. 5-FU dosage was decreased in ten patients (36%) for grade 2 or greater stomatitis or diarrhea. Mild to moderate nausea and vomiting occurred in 66% of patient trials in which no pretreatment antiemetics were administered. Other toxicities included phlebitis from 5-FU in 71%, skin toxicity in 11%, mild alopecia in 25%, and fatigue in 54% of patients. Nephrotoxicity (creatinine greater than 2.0 mg/dL) occurred in one patient. The dose of carboplatin resulting in grade 2 toxicity was 180 mg/m2 in one patient, 240 mg/m2 in one, 300 mg/m2 in seven, 360 mg/m2 in ten, and 420 mg/m2 in one. Based on these results, we recommend a starting dose of carboplatin, 300 mg/m2, in combination with five days of continuous infusion 5-FU. In this dose and schedule, this combination was well tolerated and demonstrated antitumor activity in head and neck cancer. To confirm these promising results, a Southwest Oncology Group prospective randomized trial is in progress comparing carboplatin and 5-FU, cisplatin and 5-FU, and standard-dose weekly methotrexate in recurrent-disease patients.
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PMID:A phase I-II trial of carboplatin and 5-fluorouracil combination chemotherapy in advanced carcinoma of the head and neck. 354 42

Natural interferon-alpha preparation "Sumiferon" was recently developed in Japan. This is a human lymphoblastoid interferon (HLBI) preparation. Like other interferon preparations, this preparation showed both direct and indirect antitumor effect and the toxicities were moderate. The phase I-II studies were carried out in 38 major institutions in Japan. In the phase I study in 5 patients with advanced breast cancer, the maximum tolerated dose (MTD) was found to be 12 X 10(6) units/day given for 1 month. In the phase II study, HLBI was given in at 3 approximately 6 X 10(6) units/day. Out of 391 cases, 280 were evaluable. Complete and partial responses (CR and PR) were observed in 40 (14.3%) out of 280 evaluable cases, including 11 (19.6%) out of 56 renal cell cancer, 14 (19.2%) out of 73 multiple myeloma, and 9 (17.3) out of 52 malignant lymphoma among others. Major side effects observed were: fever (69.8%), gastrointestinal disturbances (31.4%), leukopenia (30.7%), thrombocytopenia (27.8%), hepatotoxicities (23.6%) and general fatigue (22.1%). Sumiferon seemed to be one of useful antitumor drugs effective against renal cancer.
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PMID:[Introduction of natural interferon-alpha "Sumiferon"]. 363 77

Triglycidylurazol is a teroxirone derivative proposed for clinical trials on the basis of a broad spectrum of activity against murine tumors and a reduced potential for toxic manifestations at the injection site as compared to the parent compound. This phase I trial was designed to define the maximum tolerated dose of triglycidylurazol given by iv bolus on a 5-day schedule. Twenty-eight adult patients with a variety of solid tumors were entered. Their median performance status was 2 (range, 0-3), and most had received prior radiotherapy, chemotherapy, or both. A median of one course (range, one to four) was administered, for a total of 47 courses. Doses were escalated from 6 to 250 mg/m2/day. Leukopenia and thrombocytopenia were dose-related and -limiting, with a strong suggestion of increased myelosuppression with repeated courses. Nonhematologic toxic effects were generally mild to moderate. Nausea and vomiting were experienced by most patients. Local toxic effects consisting of venous discoloration, phlebitis, and/or sloughing were encountered in about one-half of the patients. Possible drug-related impairments in liver function were noted in three patients. Negligible alopecia and fatigue were also observed. Antitumor effect was detected in one patient with adenocarcinoma of unknown origin. A dose of 200 mg/m2/day for 5 consecutive days may be recommended for phase II trials.
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PMID:Phase I study of triglycidylurazol given on a 5-day i.v. schedule. 370 9

Twelve homosexual patients with Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon [Burroughs Wellcome, Research Triangle Park, NC]). They were given a dose of 20 X 10(6) U/m2 intramuscularly daily for approximately two months. Responders continued their treatment on a maintenance schedule of 20 X 10(6) U/m2 three times a week. Four patients experienced complete remissions, and four experienced partial remissions that resulted in a total response rate of 67%. The median duration of treatment was 14 weeks (7 to 28+ weeks), and the median response duration was 28+ weeks (19 to 29+ weeks). Of the four patients in complete remission, one relapsed at 25 weeks and one at 26 weeks; the other two remained in complete remission at 28 and 29+ weeks. The clinical toxicity consisted of chills, fever, fatigue, and asthenia. Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia. Asthenia, a condition present in all 12 patients, was severe in 50%. A minimal tumor burden, the absence of circulating interferon before treatment, and a performance status of greater than or equal to 90% on the Karnofsky scale were related to an improved response rate. Measurement of immunologic parameters showed significant declines in the already impaired T cell levels, lymphocyte blastogenic response to concanavalin A, monocyte-mediated antibody-dependent cellular cytotoxicity, and monocyte-adherence. Activation of natural killer cells was not noted, and no life-threatening infections occurred during treatment. These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposi's sarcoma, and its use warrants further study in a larger number of patients.
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PMID:Treatment of acquired immunodeficiency syndrome--related Kaposi's sarcoma with lymphoblastoid interferon. 387 49

A phase II study of recombinant interferon alpha A (Ro 22-8181) for malignant brain tumors was jointly conducted at 21 medical institutes in order to evaluate its clinical effects and side effects. Treatment started with exclusive administration of Ro 22-8181 at 3 X 10(6) U/day, which was increased appropriately after confirmation of its safety, until an optimum dose permitting long-term administration was achieved for each patient. The dose thus determined was intramuscularly administered daily. Among those treated, 39 patients were available for evaluation. The percentage of partial responses according to the "Criteria for the Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumor" by Koyama and Saito was 10.3% (4/39). Histologically, this was 7.1% (1/14) for glioblastoma and 14.3% (3/21) for malignant astrocytoma. Side effects included fever (57.3%), anorexia (34.1%), general fatigue (31.7%), leukopenia (52.4%) and thrombocytopenia (30.5%), and increased GOT and GPT (40.2%). In view of the success even in previously treated patients, and the side effects observed, Ro 22-8181 may be accepted as a useful addition to the treatment of malignant brain tumors.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in malignant brain tumors]. 388 62

Eighteen patients with advanced metastatic gastrointestinal cancer (stomach cancer 7, liver cancer 9, pancreas cancer 2) were treated with human recombinant interferon alpha-2 at doses of 3.0 X 10(6)-10.0 X 10(6) IU/body i.m. daily or every second day, 30 X 10(6) IU/body for five consecutive days every four weeks, or 30 X 10(6) IU/body once weekly. No tumor response was demonstrated in any of our cases. Among fifteen evaluable cases, nine had stabilization of evaluable disease at four weeks, but six showed progressive disease. On the other hand, fever, chills, fatigue, anorexia, nausea and vomiting were pronounced. In two cases, CNS toxicities developed. In some instances, leukopenia, thrombocytopenia, decrease of hemoglobin content and elevation of transaminase were observed. According to these findings, single use of recombinant interferon alpha-2 at the dose schedule outlined above does not seem to be of use for the treatment of advanced gastrointestinal cancer.
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PMID:[Phase II studies of interferon alpha-2 Sch 30500 in advanced gastrointestinal carcinoma]. 389 54

A phase I study of VP was undertaken using the methods of a single (40 cases; range of dose levels 30-540 mg/m2) and 5-day (41 cases; range of dose levels 40-140 mg/m2/day) intravenous administration. The dose-limiting toxicity of VP was moderate to severe leukopenia. MTD was estimated to be 540 mg/m2 for a single and 140 mg/m2/day for 5-day administration. The median days to WBC nadir from the start of therapy and to recovery from reaching the nadir were 10 and 10.5 for single, and 15 and 7 for 5-day administration, respectively. Thrombocytopenia was less frequent and less pronounced than leukopenia. Mild gastrointestinal disturbances and alopecia were frequently observed. Transient hepatic dysfunction, fever, headache, fatigue, dyspnea, hypotension, and pain along the vein were also encountered in a small number of patients. There were no cases with renal, neurologic or cardiac toxicity. Objective tumor regression was seen in one case each of IBL(CR), bladder cancer, non-Hodgkin's lymphoma and ATL (PR). The post-infusion plasma decay of VP in 4 cases given 80-120 mg/m2 by a single administration was biphasic with t1/2 alpha ranging from 0.13 to 0.39 h and t1/2 beta ranging from 3.33 to 4.85 h. No accumulation of VP was found in plasma after five repeated daily doses. Doses of 360-480 mg/m2 by single and 80-100 mg/m2/day by 5-day administration repeated every 3 to 4 weeks can therefore be recommended for phase II studies in good-risk patients.
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PMID:[A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration]. 394 9

Recombinant leukocyte A interferon is a highly purified single molecular species of alpha-interferon prepared by recombinant DNA methods. In 1982, a phase II trial to evaluate the efficacy of recombinant leukocyte A interferon for patients with previously treated chronic lymphocytic leukemia was begun, and 19 patients were entered in this study. Patients received one of two dose schedules depending on their pretreatment platelet counts. Those with platelet counts greater than 100,000/mm3 received 50 X 10(6) units/m2 intramuscularly three times weekly, with dose reductions to 25 X 10(6) units/m2 and 5 X 10(6) units/m2 for unacceptable toxicity. Those with platelet counts less than 100,000/mm3 received 5 X 10(6) units/m2 intramuscularly three times weekly. Toxicity was dose-dependent and included fever, chills, fatigue, anorexia, myalgias, headache, leukopenia, and thrombocytopenia. Response was evaluable in all but one of the patients entered in this study. Two of the 12 patients treated with 50 X 10(6) units/m2 had a partial response, three had no response, and seven had progressive disease. Of the six patients starting at 5 X 10(6) units/m2 in whom response was evaluable, two had no response and four had progressive disease. Five patients with progressive disease (three at 50 X 10(6) units/m2 and two at 5 X 10(6) units/m2) had an acceleration of disease while receiving recombinant leukocyte A interferon. It is concluded that the dose and schedule of recombinant leukocyte A interferon therapy tested in this study are not effective in previously treated patients with advanced chronic lymphocytic leukemia.
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PMID:Phase II trial of recombinant leukocyte A interferon in patients with advanced chronic lymphocytic leukemia. 397 47

Amrinone, a new inotropic agent, was used to treat 24 patients with chronic congestive heart failure who were classified as clinically stable and who were in New York Heart Association's classes II and III. Patients were treated for up to 30 months (mean, 12.5 months). Exercise tolerance improved in 20 patients, but only eight experienced significant improvement in symptoms of fatigue, dyspnea, and orthopnea and only nine tolerated the drug without apparent side effects. Eight were unable to continue amrinone therapy because of limiting side effects. The most significant adverse effects were cardiac arrhythmias, thrombocytopenia, abnormal results of liver function tests, diarrhea, fever, and nausea. Amrinone has a narrow therapeutic-toxic ratio, but a significant proportion (42%) of patients tolerate and benefit from amrinone therapy.
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PMID:Clinical effects and side effects of amrinone. A study of 24 patients with chronic congestive heart failure. 399 60

A clinical Phase I study of recombinant human interferon alpha A (Ro 22-8181) was performed in patients with malignant tumors; twenty of them received an American product and seven others a domestic product. Both products were administered in single intramuscularly injected doses of 18, 36, 50, 75 and 100 X 10(6)U. Main side effects included fever and influenza-like symptoms (headache, chill/shivering, general fatigue, lumbago), and digestive symptoms (anorexia, nausea/vomiting). Numbness of fingers or limbs and somnolence were also observed in higher dose groups, but these symptoms all disappeared on the day of administration or by the 3rd day after administration. Abnormal laboratory findings included leukopenia, granulocytopenia, lymphocytopenia, thrombocytopenia and increased GOT/GPT/LDH, but these returned to normal by the 10th day after administration. The peak blood concentration was correlated with the dose, falling to the base line 72 hr after administration. The American product and the domestic product were nearly comparable in the type and incidence of their side effects, and also produced generally comparable blood concentrations. Furthermore, increased anti-IFN-alpha antibody titer was not observed in any of the patients; and the Prick Test proved negative in all of them. No significant changes were observed in any immunological parameters, either.
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PMID:[Phase I study of recombinant human interferon alpha A (Ro 22-8181) in patients with malignant tumors]. 400 81


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