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)

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) generally are rapidly eliminated from the blood after intermittent intravenous infusion. Subcutaneous administration of these agents results in lower peak concentrations but is associated with prolonged systemic exposure. Elimination of the factors appears to occur by several mechanisms, including white blood cell receptor-mediated endocytosis, metabolism by proteases, and urinary excretion by glomerular filtration with subsequent reabsorption and catabolism. The pattern and route of elimination are affected by type of factor and dosage, degree of glycosylation, renal function, and number of white blood cell receptors for the particular CSF. Granulocyte CSF and GM-CSF are approved for use in patients with nonmyeloid malignancy who are receiving myelosuppressive chemotherapy, and those undergoing high-dose chemotherapy and bone marrow transplantation, respectively. In these indications, treatment generally is initiated no earlier than 24 hours after chemotherapy and continued beyond the expected chemotherapy-associated neutrophil count nadir. Limited information suggests that subcutaneous administration is more effective than intermittent intravenous infusion. The latter may require the addition of albumin to ensure stability. Storage and handling guidelines include preventing exposure to extreme temperatures and avoiding excessive agitation of the solution.
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PMID:Pharmacokinetics and administration of colony-stimulating factors. 159 12

Interleukin-2 (IL-2) has been shown to produce durable complete remission in patients with renal cell carcinoma (RCC). A phase 2 study was conducted to evaluate the potential therapeutic synergy as well as the toxic side effects of the concurrent administration of IL-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced stage disease. Twenty-one patients with unresectable or metastatic RCC having an Eastern Oncology Cooperative Group performance status of 0 or 1 were enrolled. Six patients had received prior immunotherapy with interferon (IFN)-alpha, IFN-gamma, and IL-12, whereas the remaining 15 subjects were previously untreated. Thirteen patients were assigned to a moderate-dose bolus of IL-2 at 72,000 IU/kg every 8 hours on days 1 through 5 and days 15 through 19, whereas 8 patients were given IL-2 as an intravenous continuous infusion at a dose of 5 MU/m2/d on days 1 through 5 and days 15 through 19. Subcutaneous GM-CSF at 125 microg/d on days 1 through 21 was administered concomitantly with IL-2. The median number of IL-2 bolus doses was 23 of a scheduled 28 (85%), whereas with the continuous infusion, 93% of planned IL-2 was given. All patients received 100% of GM-CSF doses. There were no complete or partial responses in this study. Of 13 patients treated in the bolus IL-2 arm, 10 had systemic progression of disease at 4 to 8 weeks, 1 developed metastasis in the brain at 4 weeks, and 2 had stable disease for 4 and 17 months. Among the 8 subjects treated with continuous infusion IL-2, 3 progressed with brain lesions at 3 to 8 weeks and 5 had stable disease at 6+, 7, 8+, 15+, and 17+ months. The median survival for the whole group was 10 months, with a range of 0.5 to 40+ months. There were no regimen-related deaths, and most of the observed toxicities were grade 1 and 2. Serious toxicities (grade 3 and 4) included anemia, atrial fibrillation, oliguria, abnormal liver function, and neurologic events like agitation or confusion. The combination of recombinant IL-2 and GM-CSF administered in the designed schedule and doses was not effective in patients with metastatic RCC and may even interfere with the therapeutic potential of moderate-dose IL-2 and increase its adverse events.
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PMID:A phase 2 study of moderate dose interleukin-2 and granulocyte-macrophage colony-stimulating factor in patients with metastatic or unresectable renal cell carcinoma. 1622 75