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)

To investigate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in patients with acute myelogenous leukaemia, a multicentre randomized study was performed. From October 1993 to September 1996, 270 patients with newly diagnosed acute myelogenous leukaemia were randomized to G-CSF or control groups after remission induction therapy. The G-CSF group received G-CSF (Filgrastim) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1.5 x 10(9)/l. The control group did not receive G-CSF unless severe infection occurred. There were 245 evaluable patients (120 and 125 in the G-CSF and control groups respectively). The complete remission rate was similar in the G-CSF and control groups (80.8% versus 76.8%), as was the 5-year probability of disease-free survival (34.5% versus 33.6%) and overall survival (42.7% versus 35.6%). Neutrophil recovery was significantly faster in the G-CSF group than in the control group (12 d versus 18 d, P = 0.0001). The median duration of febrile neutropenia was significantly shorter in the G-CSF group than in the control group (3 d versus 4 d, P = 0.0001). In conclusion, prophylactic administration of G-CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy.
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PMID:Efficacy of granulocyte colony-stimulating factor in the treatment of acute myelogenous leukaemia: a multicentre randomized study. 1184 2

The development of the therapeutic roles of filgrastim and sargramostim over the past decade is reviewed. Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), and sargramostim, a recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), have been available in the United States for over a decade to treat various types of neutropenia. In addition, data are available to support their use in a variety of clinical settings. Because of the high cost of these agents, clinical guidelines for their appropriate use have been developed. With respect to the comparability of filgrastim and sargramostim, the American Society of Clinical Oncology recommends that additional data be generated since current data are insufficient to adequately address this question in each clinical setting. A limited number of randomized, comparative trials have directly compared filgrastim with sargramostim. Outcomes data from these trials are reviewed. Further, there is evidence to suggest that, at least for GM-CSF, tolerability is dependent on the degree of protein glycosylation. A nonglycosylated protein, molgramostim, available in Europe appears to be associated with greater toxicity in clinical trials, although randomized comparative trials are lacking. The therapeutic equivalence of CSFs requires further study. While data show that the efficacy and tolerability of CSFs are similar in certain settings, there has been no definitive, randomized, large-scale clinical trial conducted to address this issue. Pharmacists should continue to evaluate clinical data to determine not only which CSF to use but also when a CSF should be used.
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PMID:Clinical applications of colony-stimulating factors: a historical perspective. 1194 13

Filgrastim, or granulocyte colony-stimulating factor, reverses neutropenia associated with human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) infections. During a trial of anti-CMV retinitis therapies coadministered with antiretroviral therapy, 2-4 plasma specimens of HIV-1 RNA were collected from 36 HIV-1-infected patients receiving filgrastim to prevent neutropenia and from 36 patients not receiving filgrastim. For both groups, the crude mean and mean rate of change of HIV-1 log(10) RNA levels were similar. Adjustment for covariates (CD4(+) T cell lymphocytes, virus load at enrollment, level of neutropenia and antiretroviral therapy [mainly non-highly active antiretroviral therapy], and anti-CMV therapy during follow-up) resulted in a mean log(10) HIV-1 RNA level for individuals receiving filgrastim versus those not receiving the drug of 5.11 versus 4.87 (P=.12) and respective log mean rates of change per month of -0.08 versus -0.21 (P=.08). This latter difference has borderline statistical significance, which suggests that filgrastim may reduce the decline of HIV-1 RNA loads.
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PMID:Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis. 1223 43

In acute lymphoblastic leukemia (ALL), treatment with granulocyte colony stimulating factor (G-CSF) during remission induction shortens granulocytopenia and may decrease morbidity due to infections. However, the optimal timing of G-CSF administration after chemotherapy is not known. In a prospective randomized multi-center study, adult ALL patients were treated with high-dose ARA-C [HDAC, 3 g/m(2) bid (1 g/m(2) bid for T-ALL) days 1-4] and mitoxantrone (MI 10 mg/m(2) days 3-5). They were randomized to receive recombinant human G-CSF (Lenograstim) 263 micro g/day SC starting either from day 12 (Group 1) or day 17 (Group 2). Fifty-five patients (41 male, 14 female) with a median age of 34 years (range: 18-55 years) were enrolled into the study; 50 patients were evaluable. The median duration of neutropenia <500/ micro l after HDAC/MI was 12 days (range: 7-22 days) in the early G-CSF Group 1 and also 12 days (range: 4-22 days) in the late G-CSF Group 2; this was shorter than in the historical control group (15 days, range: 4-43 days, n=46) where the patients received identical cytotoxic treatment without G-CSF. Seventeen infections were observed in 14 patients in Group 1 (47%) and 13 infections in 10 patients in Group 2 (50%) compared to 27 infections in 49 patients of the historical control (54%). In Group 1, the patients received a median of 11 injections with G-CSF (range: 7-22) compared to 7 injections (range: 4-19) in Group 2. The total administered dose of G-CSF in Group 2 was significantly reduced by 40% ( P<0.0001). The delayed start of G-CSF after HDAC/MI in ALL achieves the same clinical benefit compared to the earlier initiation of G-CSF. The reduction of treatment costs by reducing the total G-CSF dose may be important in future treatment with this hematopoietic growth factor.
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PMID:Prospective randomized trial to evaluate two delayed granulocyte colony stimulating factor administration schedules after high-dose cytarabine therapy in adult patients with acute lymphoblastic leukemia. 1242 38

Treatment- and disease-related neutropenia are associated with a number of negative clinical effects such as febrile neutropenia, documented infection, hospitalisation for infection-related morbidity, infection-related mortality, and decreased ability to administer the planned chemotherapy dose on schedule. Reductions or delays in dosage have the ability to jeopardise the effectiveness of treatment by lowering response rates. Not only are clinical outcomes adversely affected, but these complications can have a negative influence on patient quality of life. Filgrastim is a haematopoietic growth factor that primarily acts to stimulate the proliferation and differentiation of neutrophil progenitor cells. Filgrastim is capable of reducing the incidence and severity of neutropenia and the complications that accompany it in patients with cancer or HIV infection. Although there are few data evaluating the effect of treatment with granulocyte colony-stimulating factor on quality of life, it is assumed that the benefits would be seen through both the reduction of treatment-related complications and the enhanced potential for long-term disease control. A new, longer-acting form of filgrastim is now available that has the potential to simplify the management of neutropenia and further improve patient quality of life by decreasing the number of necessary injections. Additional prospective controlled trials that contain quality-of-life issues as endpoints are needed.
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PMID:Filgrastim in patients with neutropenia: potential effects on quality of life. 1247 95

Myeloablative or high-dose chemotherapy regimens utilise doses that are significantly greater than those used in standard treatments. The neutropenia caused by these high-dose therapies can be associated with an increased incidence of bacterial and fungal infections and remains an important clinical issue among patients with advanced-stage cancers. Filgrastim is approved for stem cell mobilisation in both chemotherapy-treated patients and normal donors. Harvested peripheral blood progenitor cells have been used effectively in allogeneic and autologous transplantation, increasing the speed and extent of neutrophil and platelet recovery. Accelerated haematopoietic recovery is associated with a significantly shorter hospital stay and, therefore, leads to a reduction in treatment costs. The contribution of filgrastim to the acceleration of haematopoietic recovery after peripheral blood progenitor cell transplant has been assessed in a number of prospective clinical trials after high-dose chemotherapy. Controversy remains over whether growth factors should be administered shortly after stem cell infusion or after several days. The recently approved, once-weekly form of filgrastim, pegfilgrastim, has been shown to have efficacy comparable to that of the native molecule and can be expected to enhance patient quality of life through the need for fewer injections. This article will review the role of filgrastim for stem cell mobilisation and transplantation in patients receiving high-dose chemotherapy.
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PMID:Use of filgrastim for stem cell mobilisation and transplantation in high-dose cancer chemotherapy. 1247 96

Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than 0.5 x 10(9)/L, lasting for months or years. Congenital, cyclic, and idiopathic neutropenia are principal categories of SCN. Since 1994, the Severe Chronic Neutropenia International Registry (SCNIR) has collected data to monitor the clinical course, treatments, and disease outcomes for SCN patients. This report summarizes data for 853 patients, almost all treated with daily or alternate-day recombinant human granulocyte colony-stimulating factor (G-CSF or Filgrastim). G-CSF treatment increased the ANC overall from 0.34 x 10(9)/L +/- 0.018 pre-treatment to 3.70 x 10(9)/L +/- 0.18 during the first year of treatment. For most patients, the responses were durable with patients remaining on the same dose of G-CSF for many years. Long-term hematological observations showed stable mean leukocyte and neutrophil counts and gradually increasing hemoglobin levels. Thrombocytopenia developed in 4% of patients. As of January 1, 2000, myelodysplasia (MDS) or acute myelogenous leukemia (AML) has occurred in 35 of 387 patients with congenital neutropenia with a cumulative risk of 13% after 8 years of G-CSF treatment. This event occurred without a predictable relationship to the duration or dose of G-CSF treatment. No patients with cyclic or idiopathic neutropenia developed MDS or AML. Other important adverse events included hepatomegaly, osteoporosis, vasculitis, glomerulonephritis, and deaths in 4 of 14 cases requiring splenectomy. Growth and development and the outcome of pregnancy appeared to be unaffected by G-CSF treatment. These data indicate that congenital, cyclic, and idiopathic neutropenia can be effectively treated with long-term G-CSF. The risk of leukemia, osteoporosis, other potentially adverse events, and pregnancy outcome need to be further evaluated with continuing long-term observations.
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PMID:Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. 1255 10

Many chemotherapy regimens cause myelosuppression, which can result in febrile neutropenia and potentially lead to serious infections. The risk of neutropenia and its complications can be reduced with filgrastim, a granulocyte-colony-stimulating factor. Filgrastim is safe and effective, but it is cleared rapidly from the body (predominantly through the kidneys) and requires daily administration for up to 14 days. A pegylated form of filgrastim, pegfilgrastim, has been developed by attaching a polyethylene glycol molecule to filgrastim. Pegfilgrastim has an extended circulation half-life and self-regulating, patient-specific pharmacokinetics, making it possible to give the treatment as a single dose once per chemotherapy cycle. Clinical trials have shown that a single, subcutaneous dose of pegfilgrastim is as safe and effective as daily filgrastim injections in patients treated with myelosuppressive chemotherapy. In addition, a single, 6 mg fixed dose of pegfilgrastim per chemotherapy cycle is sufficient in adult patients, regardless of their body weight, making pegfilgrastim a simple, effective, and well-tolerated option for managing chemotherapy-induced neutropenia.
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PMID:Pegfilgrastim for chemotherapy-induced neutropenia. 1262 35

This combined, retrospective analysis compared once-per-chemotherapy-cycle pegfilgrastim with daily Filgrastim in breast cancer patients undergoing myelosuppressive chemotherapy enrolled in two similarly designed, randomized, double-blind, pivotal trials. On day 2 of each chemotherapy cycle, a single subcutaneous (SC) injection of pegfilgrastim [either 6 mg (n=77) or 100 microg/kg (n=149)] was administered, or daily Filgrastim SC injections (5 microg/kg/day; n=222) were initiated and continued until either absolute neutrophil count (ANC) > or =10 x 10(9)/l after the expected nadir or for up to 14 days, whichever occurred first. Individually, each of these trials demonstrated that a single pegfilgrastim injection per cycle is as effective at reducing the duration of severe neutropenia as daily injections of Filgrastim. Clinical efficacy data from the two trials were combined for analysis (n=448). The risk of febrile neutropenia (FN; absolute neutrophil count <0.5 x 10(9)/l with fever > or =38.2 degrees C) was significantly lower [11% vs 19%, respectively; relative risk = 0.56 (95% confidence interval: 0.35, 0.89)] in patients receiving pegfilgrastim than for those receiving Filgrastim. Trends towards lower risks of hospitalization and intravenous anti-infective use were also observed. These observations were consistent irrespective of risk factors, including age, disease stage, performance status and prior treatment. Pegfilgrastim may offer patients more effective protection against neutropenic complications of chemotherapy with fewer injections and less disruption to their lives.
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PMID:A combined analysis of two pivotal randomized trials of a single dose of pegfilgrastim per chemotherapy cycle and daily Filgrastim in patients with stage II-IV breast cancer. 1268 49

Pyrazoloacridine (PZA, NSC366140, PD115934) is an acridine derivative currently undergoing clinical evaluation. In preclinical testing, PZA has shown selectivity for solid tumor cell lines, activity in hypoxic, noncycling, and multidrug-resistant cell lines, and synergy with cisplatin in a variety of lung cancer cell lines. In early phase I clinical studies PZA has shown modest activity in ovarian, cervical, and colon cancer. The purpose of the present study was threefold: to determine the maximally tolerated doses of the combination of PZA (3-h infusion) and cisplatin administered with and without Filgrastim (G-CSF) (Amgen, Thousand Oaks, CA) every 3 weeks in untreated or minimally pretreated patients, to describe and quantify the clinical toxicities of combination chemotherapy with PZA and cisplatin, and to evaluate the effects of drug sequencing on the toxicity profile and pharmacologic behavior of PZA. The starting doses in this dose-escalation trial were PZA 400 mg/m2 as a 3-h intravenous infusion and cisplatin 50 mg/m2 as a 1 mg/min intravenous infusion. The sequence of drugs was alternated with each successive course in each patient treated. Twenty-one patients with refractory solid tumors received 43 courses of therapy through four dose levels. Neutropenia was dose-limiting and defined the maximum tolerated dose of PZA 400 mg/m2 and cisplatin 50 mg/m2 without G-CSF support. With G-CSF support, nausea and vomiting were dose-limiting. The maximum tolerated and recommended doses for further study of this combination are PZA 600 mg/m2 over 3 h and cisplatin 50 mg/m2 followed by G-CSF support. Pharmacokinetic analysis showed that sequence does not impact on the pharmacokinetics of PZA when given in combination with cisplatin.
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PMID:A phase I and pharmacologic study of pyrazoloacridine and cisplatin in patients with advanced cancer. 1279 32


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