Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, 18 patients with advanced breast cancer were treated with multiple cycles of doxorubicin (75 or 90 mg/m2) plus cyclophosphamide (750 or 1000 mg/m2) every 21 days. Granulocyte-macrophage colony-stimulating factor (GM-CSF) (250 micrograms/m2 per day) was administered by continuous infusion during 10 days (days 2-12), starting in the first or second cycle of chemotherapy. Sixteen (89%) of 18 patients (95% confidence interval, 65%-99%) achieved an objective remission, five (28%) of which were complete. The median duration of response was 7 months. When GM-CSF was used for the first time, it had an effect on the kinetics of all blood cells, including neutrophils, lymphocytes, thrombocytes, and reticulocytes. However, in subsequent cycles of chemotherapy, the stimulatory effect of GM-CSF on hematopoiesis was substantially diminished. World Health Organization grade 3 and 4 neutropenia and thrombocytopenia necessitated dose reductions of doxorubicin and cyclophosphamide from cycle 2 onward in all patients treated with the highest dose. Side effects of GM-CSF included fever, general weakness, and hypotension. These toxic effects mimicked sepsis, and hospital admission for treatment with intravenous antibiotics was required for 73 days in 61 cycles of chemotherapy that included GM-CSF. Dose-intensive chemotherapy produced a high response rate in patients with advanced breast cancer. However, GM-CSF administered from day 2 to day 12 at a dose of 250 micrograms/m2.
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PMID:Effects of recombinant human granulocyte-macrophage colony-stimulating factor on myelosuppression induced by multiple cycles of high-dose chemotherapy in patients with advanced breast cancer. 196 Jul 51

Patients may be intolerant of zidovudine for several reasons, the most prominent being hematologic toxicity. In vitro studies demonstrate that zidovudine is toxic to the myeloid and erythroid precursors in the bone marrow; at concentrations of zidovudine near those associated with the optimal antiviral effect in vitro, the proliferative capability of these progenitor cells is reduced 50%-70%. The clinical manifestations of anemia and leukopenia generally are time- and dose-dependent. Strategies for alleviating the hematologic toxicity of zidovudine include the use of hematopoietic growth factors, such as erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Myopathy, a recently recognized toxic effect of zidovudine, also appears to be time-dependent. Patients often complain of muscle weakness and discomfort and exhibit an associated elevation in creatine phosphokinase level; dose reduction or discontinuation of therapy generally is required. Some patients have experienced high fever, nausea, and vomiting; however, these effects are unusual and of unclear etiology. The substantial proportion of patients with AIDS or AIDS-related complex receiving zidovudine who experience hematologic or muscular toxicity may benefit from treatment with new antiviral agents, such as dideoxyinosine, with toxicity profiles different from that of zidovudine.
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PMID:Zidovudine intolerance. 220 Oct 71

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral nerve dysesthesias, myalgias, and weakness. Dose-limiting toxicity was observed at 60 mg/m2 and consisted of severe hypertension, hypotension, and atrial fibrillation in one patient each, respectively. Significant increases in white blood cell count, granulocyte count, eosinophil count, and monocyte count occurred after rhGM-CSF treatment. Significant enhancement of in vitro and in vivo monocyte and neutrophil tumoricidal activity and antibody-dependent cellular cytotoxicity along with significant elevations in C-reactive protein and neopterin were observed. Despite these immunological and biological changes, no antitumor activity was seen. In short, the combination of ch14.18 and rhGM-CSF resulted in toxicity similar to that observed with ch14.18 alone without improvement in tumor response.
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PMID:Phase Ia/Ib trial of anti-GD2 chimeric monoclonal antibody 14.18 (ch14.18) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in metastatic melanoma. 881 95