Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to determine the maximum tolerated dose (MTD) of epirubicin combined with a fixed dose of paclitaxel, without and with support of filgrastim, in patients with platinum resistant or refractory ovarian cancer. Paclitaxel (150 mg/m2) and epirubicin (starting dose 90 mg/m2, 15 mg/m2 escalation per level) were given on day 1, every 28 days for 4-6 cycles. Filgrastim (F) (5 microg/kg/die) was given in case of grade 4 leukopenia (levels without support) or from day 4 up to leukocyte count >10,000/mm3 after nadir (levels with support). Cohorts of 3 patients were enrolled at each level and further 3 patients were planned if 1 or 2 unacceptable toxic events (UTE) were registered. MTD was determined first without and then with filgrastim. Four levels were studied (90, 90+F, 105+F, 120+F) with 4, 6, 5 and 4 patients enrolled, respectively. UTE (grade 4 neutropenia) were observed in 3 patients at level 1. Thus, 90 mg/m2 was the MTD for epirubicin without filgrastim. MTD of epirubicin with filgrastim was not reached at 120 mg/m2. Hematological toxicity was mild. Grade 3 mucositis was reported in 1 patient. Among the 14 patients with measurable or evaluable disease, 3 objective responses were observed (1 complete and 2 partial) for an overall response rate of 21.4%. The combination of paclitaxel 150 mg/m2 and epirubicin at 120 mg/m2 with filgrastim is a feasible therapy. Grade 4 leukopenia is the dose limiting toxicity using epirubicin at 90 mg/m2 without filgrastim.
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PMID:A phase I study of paclitaxel and epirubicin, without and with filgrastim, for the treatment of platinum-resistant advanced ovarian cancer. 1034 89

Multifractionated dosing (MFD) schedules for chemotherapy administration such as weekly or twice weekly administration are intended to maximize dose intensity while minimizing toxicity, but the cumulative drug effect may result in neutropenia necessitating interruption of dose fractions and thereby compromising dose intensity. Intermittent granulocyte colony-stimulating factor (G-CSF, Neupogen, Amgen) was administered to patients receiving MFD on three paclitaxel-based chemotherapy regimens. Single-dose G-CSF was administered concomitant with the chemotherapy dose fraction when the white blood count was between 2000 and 3500 cells/microliter. A retrospective analysis of the concomitant administration of single-dose G-CSF with chemotherapy in these trials demonstrated that in most patients, G-CSF administration guided by the level or grade of leukopenia permitted maintenance of the chemotherapy dose intensity and completion of the treatment cycle. The common pattern in a six-dose, twice weekly, multifractionated cycle was for G-CSF to be administered with every other chemotherapy dose beginning with the third, fourth, or fifth dose, but some courses required G-CSF administration with each chemotherapy dose fraction. Guidelines for the concomitant use of G-CSF and paclitaxel-based MFD chemotherapy can be used to maintain chemotherapy dose intensity. A prospective study of guidelines for cytokine usage developed on the basis of this retrospective study will be necessary to determine the optimal cytokine dose and schedule for use simultaneously with chemotherapy.
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PMID:Single-dose granulocyte colony-stimulating factor concomitant with multifractionated dose chemotherapy: a strategy for maintaining dose intensity. 1051

Hematopoietic growth factors are well known to increase neutrophil counts and support the administration of myelotoxic and myelosuppressive therapies, especially chemotherapies. Filgrastim (r-metHuG-CSF) has been used in the setting of HIV disease to treat neutropenia and HIV-associated neutrophil defects. This article reviews the biology, product characteristics, and preclinical and clinical development of Filgrastim. Emphasis is given on the use of Filgrastim in the setting of HIV infection and AIDS.
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PMID:Biopharmaceutical drug development: Filgrastim (r-metHuG-CSF) use in patients with HIV infection. 1059 29

Neutropenic individuals are at high risk for bacterial and fungal infections. Filgrastim (r-metHuG-CSF, NEUPOGEN) has been shown to improve chemotherapy-induced neutropenia significantly. Because a high incidence of HIV-infected patients have neutropenia, often associated with myelosuppressive antiretroviral medication, Filgrastim is frequently used as a treatment strategy for this HIV-associated neutropenia. This review summarizes published work related to the use of Filgrastim in HIV-infected patients. Literature bases (EMBASE, MEDLINE, Int. Pharm. Abs., SciSearch, and Aidsline) from 1970 to 1998 were searched for articles describing the relationship of Filgrastim and ANC to bacterial infection rates, bacterial infection outcome, and overall survival. Thirty-five related articles were identified during this search. Filgrastim appears to have a significant role in increasing peripheral ANC and enhancing neutrophil function in patients with HIV infection and AIDS. This may translate into a clinical benefit of delivery of full-dose myelosuppressive antiretroviral therapy and decreased susceptibility to infections and increased survival in this patient population.
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PMID:The use of Filgrastim in AIDS-related neutropenia. 1059 30

Data have shown that neutropenia is a risk factor for severe bacterial infections. Two trials were done in HIV-infected patients to study the effect of Filgrastim on neutropenia and the incidence of severe bacterial infections. The incidence of Mycobacterium avium complex (MAC) infection in this setting was also evaluated. This paper reviews the results of these two studies, which suggest that Filgrastim is safe and effective in preventing severe neutropenia in patients with advanced HIV infection.
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PMID:Clinical experience with Filgrastim in AIDS. 1059 31

In a study of 258 moderately neutropenic HIV-infected patients, Filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) treatment significantly reduced the incidence of severe neutropenia and bacterial infections. Filgrastim-treated patients also had 54% fewer severe bacterial infections and 45% fewer days in hospital for any bacterial infections. No unexpected or new adverse events were observed and there were no differences in plasma HIV-1 RNA levels between the groups.
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PMID:Prevention of bacterial infections in patients with advanced HIV infection. 1059 77

Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (receptor mediated clearance [RMC]) predominantly on neutrophils, the second process is likely the result of renal clearance. With the intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has been made by association of Filgrastim with poly(ethylene glycol). The desired properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is shown here to sustain significantly elevated neutrophil counts in hematopoietically normal mice for 5 days. In neutropenic mice effects were noted for at least 9 days, accompanying a significant reduction in the duration of chemotherapy induced neutropenia. Normal human volunteers showed higher than baseline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34+ cells and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrastim. These data indicate that SD/01 represents an efficacious novel form of Filgrastim with actions sustained for between one and two weeks from a single injection.
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PMID:A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. 1064 90

Neutropenia frequently complicates infection due to human immunodeficiency virus (HIV). The etiology of neutropenia in this setting includes bone marrow infection or infiltration, myelosuppressive therapies, the presence of antibodies to HIV, and accelerated apoptosis. Protection against microbial invaders by neutrophils is further compromised by impaired chemotaxis and phagocytosis, production of toxic oxygen species, and expression of cellular adhesion molecules. Neutropenia is a significant risk factor for bacterial infection in HIV-infected patients. Endogenous cytokines, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor, regulate neutrophil count and function. Treatment with recombinant human methionyl G-CSF (filgrastim) has lessened neutropenia in patients with HIV infection. Clinical trials have shown that the incidence of bacterial infections and the number of consequent days of hospitalization for HIV-infected patients receiving filgrastim therapy are lower. Filgrastim treatment also allows administration of larger doses of myelosuppressive agents.
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PMID:Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: the role of granulocyte colony-stimulating factor. 1067 24

Growth factors (G-CSF Neupogen Roche i GM-CSF Leucomax Sandoz) have been applied in 133 therapeutic and prophylactic cycles in 88 children with acute leukaemias. GM-CSF and G-CSF were administered subcutaneously or intravenously at a dose of 2 to 8 micrograms/kg for 2 to 28 days. 45 prophylactic cycles had been administered in children with acute lymphoblastic leukaemia in high risk group and in relapses, which caused significant reduction in the number of infections, time of neutropenia and fever. Therapeutic cytokines cycles were applied when the absolute neutrophil count have fallen below 0.5 x 109/l. We observed significant reduction in duration of neutropenia in these cycles. Tolerance of GM-CSF and G-CSF was good. Side effects were not observed.
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PMID:[The efficacy of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of acute leukemia in children]. 1073 45

Total number of 306 cycles of GM-CSF-Leucomax Sandoz (5 mg/kg/day s.c.) and/or G-CSF Filgrastim Hoffmann-La Roche (5-10 mg/kg/day s.c.) was applied in 146 children aged from 0.5-18 years during neutropenia associated with chemotherapy of solid tumours. Seventeen children with malignancies served as a historical control group. Our study have demonstrated after both G- and GM-CSF therapy shorter period of neutropenia, reduction of the number of febrile days and a decreased frequency of infectious complications and infection's duration.
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PMID:[The efficacy of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of solid tumors in children. Report of Polish Pediatric Leukemia/Lymphoma Treatment Group]. 1073 46


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