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 combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. 190 99

The effectiveness of addition of interferon-alpha (IFN-alpha) to zidovudine in patients with AIDS-associated Kaposi's sarcoma was assessed in a non-randomized, phase II clinical trial. Twenty-one patients were treated with oral zidovudine (600 mg daily) and IFN-alpha was increased to 18 MU daily for another 4 weeks. Only one of the 20 evaluable patients achieved a partial response at 8 weeks, that lasted for 3 months. Despite IFN-alpha dose escalation in six patients, no further responses were seen. While myelotoxicity was mild, fatigue was the dose-limiting side-effect that prevented dose escalation in seven eligible patients. The combined treatment did not result in a decrease in HIV-Ag. In summary, our results indicate that the addition of IFN-alpha to zidovudine in patients with AIDS-associated Kaposi's sarcoma is not an efficacious treatment.
 ...
PMID:Combined zidovudine and interferon-alpha treatment in patients with AIDS-associated Kaposi's sarcoma. 199 61

Tumor necrosis factor (TNF) has demonstrated antitumor activity against a variety of tumors and is particularly cytotoxic to capillary endothelial cells, which are the presumed cell of origin of Kaposi's sarcoma. We evaluated the toxicity and clinical antitumor and antiretroviral effects of recombinant TNF administered at a once weekly dose of 100 micrograms/m2 intravenously for 8 weeks in five men with AIDS-related Kaposi's sarcoma and without prior opportunistic infection. One patient was removed from study at week 4 due to rapid progression of Kaposi's sarcoma, another patient with stage IV disease and a pretreatment CD4 count of 11 developed fever, hypotension, and pneumonia at week 7 and died 8 days after discontinuing recombinant TNF. No pathogenic organisms were isolated. He had marked eschar formation of his Kaposi's sarcoma lesions, particularly in areas previously exposed to radiation therapy. Uniform toxicities included fevers, rigors, and headaches during drug infusion that were ameliorated by prophylactic meperidine hydrochloride and acetaminophen. All experienced fatigue and three had arthralgias. One patient had transient hypotension which corrected with i.v. fluids. No significant hematologic, hepatic, or renal toxicities were seen. All patients had some progression of their Kaposi's sarcoma on study. There was no change in CD4 or CD8 count or in CD4:CD8 ratios. Serum human immunodeficiency virus (HIV) p24 antigen levels increased greater than 50% in three patients. We conclude that, as a single agent, at a dose of 100 micrograms/m2 recombinant TNF by i.v. infusion has no obvious antitumor or antiretroviral effects in patients with AIDS-related Kaposi's sarcoma.
 ...
PMID:Intravenous recombinant tumor necrosis factor in the treatment of AIDS-related Kaposi's sarcoma. 291 61

To assess safety, antitumor response, and immunological and virological activity of interferon-alpha 2a and zidovudine combination therapy in patients with AIDS-related Kaposi's sarcoma, we conducted an open-label, Phase II, multicenter study. Sixty-three patients with biopsy-proven Kaposi's sarcoma and no previous interferon-alpha therapy received zidovudine 600 mg/day and interferon-alpha 2a 18 x 10(6) U/day. The median duration of follow-up was 49 weeks. Of 62 evaluable patients, 25 (40%; 95% confidence interval, 0.28-0.52) showed a complete (26%) or partial (15%) antitumor response. Eight of 30 patients (27%) with < 100 CD4 cells/mm3 and 17 of 32 patients (53%) with > or = 100 CD4 cells/mm3 had a response. The median time to response was 36 weeks. Of the 25 patients with a response, four developed tumor progression. The median duration of response was 22.4 weeks. Eight patients (13%) developed another AIDS-defining event and 13 (21%) died. The major toxicities included anemia (16%), neutropenia (27%), elevated serum transaminases (16%), weight loss (16%), malaise (14%), fatigue (14%), fever (10%), and headache (6%). Therapy with intermediate-dose interferon-alpha 2a and zidovudine resulted in tumor regression in patients with AIDS-related Kaposi's sarcoma who had a wide range of CD4 cell counts; this therapy was relatively well tolerated.
 ...
PMID:A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group. 860 Dec 24