Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:BIOD00035 (CSF)
 30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous study has shown that the combination of mitoxantrone (Novantrone, NO) and Ara-C (AC) (NOAC) was active in refractory non-Hodgkin's lymphoma (NHL) but myelosuppression was dose-limiting. In a pilot study, we investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) after NOAC chemotherapy in patients with refractory NHL. NO was applied at a dosage of 10 mg/m2/day on days 2 and 3 and AC at 3 g/m2/12h on days 1 and 2. RhGM-CSF was administered at 250 ug/m2/day as a continuous i.v. infusion from day 6 until the neutrophils were greater than 3.0/nl for 3 consecutive days. Twenty-three patients from five of the nine participating centers were treated with NOAC chemotherapy plus rhGM-CSF, whereas 14 patients from the other four centers received chemotherapy alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nl) after NOAC was 8 days versus a median of 13 days without rhGM-CSF (P = 0.0058), and that of thrombocytopenia (less than 20.0/nl), 3 days versus 7 days (P greater than 0.4, NS). The rates of infections and stomatitis were 25% and 17%, respectively, for patients treated with rhGM-CSF as compared to 53% (P = 0.0547, NS) and 60% (P = 0.0078), respectively, without rhGM-CSF. The following side effects were associated with the administration of rhGM-CSF: pleural and/or pericardial effusions in five patients, thrombosis in two patients, bone pain in two patients, and respiratory distress syndrome in one patient. A complete remission was achieved in nine of the 23 patients treated with NOAC plus rhGM-CSF, and in two of the 14 patients treated with chemotherapy alone. The median survival of patients treated with rhGM-CSF was not reached at 400 days and seemed to be longer than that of patients treated with chemotherapy alone (median, 109 days; P = 0.036). RhGM-CSF after chemotherapy can be applied safely to patients with NHL, shorten the period of severe cytopenia, reduce the rates of stomatitis, and did not seem to cause adverse effects on response.
 ...
PMID:Mitoxantrone/high-dose Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. A pilot study. 219 41

Mitoxantrone (Novantrone, American Cyanamid Company; NO) and high-dose cytarabine (Ara-C; AC) have each been shown to be active in non-Hodgkin's lymphomas (NHL) in various studies. The studies reported here are sequential. The first study (NOAC I) combined high-dose cytarabine (3 g/m2/12 h as a 3 h infusion on day 1) with mitoxantrone (10 mg/m2/d on days 2 and 3). Of 31 patients with relapsed and refractory NHL, 7 achieved complete remission (CR) and 7, partial remission (PR). Myelosuppression was the major toxicity of this regimen. In the second study (NOAC II), the dosage of cytarabine was escalated to 3 g/m2/12 h on days 1 and 2 (4 doses) while mitoxantrone remained 10 mg/m2/d on days 2 and 3. The effects of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) were simultaneously studied. Twenty-three patients from five centers were treated with NOAC plus rhGM-CSF while 14 patients from four centers received NOAC II alone. A CR was achieved in 9 of 23 patients who received the additional rhGM-CSF and in 2 of 14 patients treated with NOAC alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nL) after chemotherapy was 8 days versus a median of 13 days without rhGM-CSF, while the duration of severe thrombocytopenia (less than 20/nL) was not significantly different. The rates of infection and mucositis were 25% and 17%, respectively, with rhGM-CSF compared to 53% and 60% without rhGM-CSF. Thus, this last nonrandomized pilot study indicates that administration of rhGM-CSF reduces the duration of chemotherapy-induced cytopenia and the rate of mucositis. This growth factor does not appear to result in stimulation of lymphoma cells. At present, a controlled randomized trial is being conducted using NOAC II with rhGM-CSF or placebo to establish the definitive role of this growth factor in the treatment of NHL.
 ...
PMID:Sequential studies on the role of mitoxantrone, high-dose cytarabine, and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of refractory non-Hodgkin's lymphoma. 225 18

Concomitant use of the monoclonal antibody-purified factor IX concentrate (Mononine, Armour Pharmaceutical Company, Collegeville, Pa.) and two antifibrinolytic agents, epsilon-aminocaproic acid (EACA; Amicar, Immunex, Seattle, Wash.) or tranexamic acid (AMCA; Cyklokapron, Kabi Pharmacia, Piscataway, N.J.) was examined for safety and efficacy in patients with hemophilia B. In a retrospective review of 19 patients treated with monoclonal antibody-purified factor IX and EACA on 35 occasions, bleeding was successfully controlled and no instances of clinical thrombotic complications were reported; one instance of urticaria resolved without additional treatment. The use of EACA or AMCA in combination with monoclonal antibody-purified factor IX was also examined prospectively in a study of 9 patients. Bleeding was effectively controlled and no thrombotic events were detected clinically with either antifibrinolytic agent. No significant changes in hematocrit or hemoglobin were detected, and there was no evidence of thrombosis as evaluated clinically and by sensitive molecular markers. It was concluded from both the retrospective and prospective data that monoclonal antibody-purified factor IX concentrate in combination with an antifibrinolytic agent does not activate the coagulation cascade and is a safe and effective treatment for prevention and control of oral bleeding in hemophilia B patients.
 ...
PMID:Concomitant treatment with factor IX concentrates and antifibrinolytics in hemophilia B. 757 94

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, +/- Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis. All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m2 subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 x 10(9)/L and 0.97 x 10(9)/L in cycle 1 as compared to 5.95 x 10(9)/L and 2.92 x 10(9)/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.
 ...
PMID:A phase II study of recombinant granulocyte macrophage colony stimulating factor in patients with non-Hodgkin's lymphoma. 795 Sep 23

In two previous studies, we observed that recombinant human interleukin-3 (IL-3) induced an increase in marrow burst-forming unit-erythroid-derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.
 ...
PMID:Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia. 794 99

The purpose of this study was to evaluate the feasibility of chronic oral administration of etoposide with granulocyte-macrophage colony-stimulating factor (GM-CSF) [sargramostim (Immunex)] coadministration or premedication; to estimate and compare the frequency of toxicities accompanying etoposide administration alone, etoposide/GM-CSF coadministration and etoposide with GM-CSF premedication. Thirty-nine patients with advanced treatment-refractory malignancies were enrolled to this study. Eligible patients were randomized to one of three treatment arms: daily oral etoposide alone for 21 days (arm A); daily oral etoposide for 21 days with GM-CSF, 250 micrograms/m2, s.c. twice daily for the first 10 days of etoposide administration (arm B); or daily oral etoposide for 21 days with GM-CSF twice daily for the sixth through second days preceding etoposide administration (arm C). Courses of treatment were repeated every 28 days. Etoposide dosages for each arm were 25, 50, 75 and 100 mg/m2/day. At least three patients were treated at each dosage level until dose-limiting toxicity was observed. Patients had twice weekly blood counts and weekly clinical examinations to assess toxicity. Patients with measurable or evaluable evidence of cancer were assessed for antitumor response after every other course of therapy. Nadir neutrophil counts at each dosage level were compared between treatment arms by non-parametric Wilcoxen rank sum tests. GM-CSF coadministration (arm B) or premedication (arm C) with daily chronic oral etoposide was feasible and did not lead to excessive hematological toxicity. Pairwise comparisons of neutrophil nadirs for the first course of therapy for each treatment arm did not demonstrate any significant differences and, at most, a slight trend favoring improved neutrophil nadirs was shown for arm C compared to arm A (p = 0.07). Dose intensity as measured by mean days of etoposide administered per patient for each arm suggested only slight improvement in etoposide tolerance for treatment arms B and C. The conclusion, GM-CSF can be safely administered to patients receiving chronic daily oral etoposide. It appears that GM-CSF provides no clinically useful improvement in granulocyte tolerance of therapy.
 ...
PMID:A randomized phase I study of oral etoposide with or without granulocyte-macrophage colony-stimulating factor for the treatment of patients with advanced cancer. 882 8

Registered nurses (RNs) and clinical pharmacists in the Hematology-Oncology Clinic at Walter Reed Army Medical Center conducted a descriptive study to determine the effectiveness and safety of using indwelling peripheral intravenous catheters (pics) for daily administration of various chemotherapeutic agents given intermittently over a 3-5 day period to outpatients. Eighty-nine adult outpatients requiring daily doses of chemotherapy including Fluorouracil (5-FU) (Solopak, Elk Grove Village, IL), Leucovorin (Immunex, Seattle, WA), Cisplatin (CDDP) (Bristol-Meyers, Princeton, NJ), Etoposide (VP-16), (Gensia, Irving, CA), Topotecan (SmithKline Beecham, Philadelphia, PA), or Taxol (Mead Johnson, Princeton, NJ), plus antiemetics were studied. Vialon 20-, 22-, or 24-gauge indwelling PICs (Becton Dickinson, Sandy, UT), were placed. Approximately 80% of patients successfully completed treatment with the original PIC in place. Daily flushing of the PIC with 2 ml [corrected] of Heplock U100 (Elkins-Sinn, Cherry Hill, NJ), maintained Heplock patency.
 ...
PMID:Use of an indwelling peripheral catheter for 3-5 day chemotherapy administration in the outpatient setting. 906 Mar 58

The stability of thiotepa in a new formulation of the drug was studied. Vials of Thioplex (Immunex), a relatively new lyophilized formulation of thiotepa, were reconstituted with sterile water and diluted with 0.9% sodium chloride injection in polyvinyl chloride infusion bags to thiotepa concentrations of 0.5, 1, and 3 mg/mL. The solutions were stored at 8 and 25 degrees C in ambient light and analyzed at 0, 8, 24, and in most cases 48 hours for thiotepa concentration and chloro-adduct formation by stability-indicating high-performance liquid chromatography. Thiotepa 1 and 3 mg/mL was stable for 48 hours at 8 degrees C and for 24 hours at 25 degrees C. Thiotepa 0.5 mg/mL was not stable at either temperature. Storage at 8 degrees C slowed but did not prevent chloro-adduct formation and loss of potency. The pH tended to increase with time; turbidity remained low. Thiotepa (lyophilized) 1 and 3 mg/mL in 0.9% sodium chloride injection was stable for 48 hours at 8 degrees C and for 24 hours at 25 degrees C; the drug was unstable when diluted to 0.5 mg/mL and stored under the same conditions.
 ...
PMID:Stability of thiotepa (lyophilized) in 0.9% sodium chloride injection. 939 20

The first morning session of the Eighth International Conference of the Inflammation Research Association was titled 'Targets in Cytokine Activation'. It encompassed four areas of research that may be considered as either current or future targets. Probably the best established target of the four is interleukin-1 beta converting enzyme (ICE) and Winnie Wong from BASF Bioresearch Corporation presented an overview of work in this field. This was followed by a newly emerging target called TACE (TNF-alpha converting enzyme) in a presentation from Douglas Cerretti of Immunex. The final two presentations covered work with chemoattractant receptors (Craig Gerard, Harvard) and mice where the inducible NO synthase gene had been deleted (John Mudgett, Merck).
 ...
PMID:Targets in cytokine activation. 942 21

von Willebrand's disease (VWD) is the most common hereditary bleeding disorder. Unchecked or improperly managed, VWD-associated hemorrhage can lead to catastrophic surgical outcome. Based on the authors' recent experience with 21 procedures in 12 patients, a contemporary protocol for successful perioperative management of VWD in otolaryngologic surgery is presented. In patients with VWD type 1 or 2a, desmopressin, a synthetic vasopressin analog, is administered both pre- and postoperatively to release von Willebrand factor (VWF) from storage sites. In type 2b or 3, a factor VIII concentrate rich in VWF is administered. In addition, a 10- to 14-day course of intravenous and/or oral Amicar (Immunex Corp., Seattle, WA) may be prescribed postoperatively. Intraoperatively, the surgical laser is used to further decrease blood loss and augment hemostasis. This medical and surgical protocol minimizes the risk of hemorrhage and of transfusion-related complications through the judicious use of preoperative and postoperative coagulation replacement products. Using these guidelines in a variety of otolaryngologic cases, the authors have had no bleeding complications at their institution.
 ...
PMID:Perioperative management of von Willebrand's disease in otolaryngologic surgery. 943 63


1 2 3 4 5 Next >>