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

Thirteen patients with recurrent medulloblastoma were treated with cyclophosphamide in association with Sargramostim. Cyclophosphamide was given at doses ranging between 1.0-2.5 g/m2 daily for two doses. Sargramostim was given at a fixed dose of 250 micrograms/m2 subcutaneously twice a day beginning 24 hours after the second cyclophosphamide dose and continuing through the leukocyte nadir until the ANC was more than 1,000 cells/microliters for two consecutive days. A total of 33 courses were given with toxicity consisting of grade 4 neutropenia in all courses and grade 3-4 thrombocytopenia in 10 of 13 patients. There were no deaths related to infection or bleeding. Four patients were taken off study because of prolonged myelosuppression. Three of these patients were at the 2.5 g/m2 level, and of these three, two developed lung toxicity (grades 2 and 4, respectively). One patient developed an allergic reaction following the first injection of Sargramostim and was also taken off study. Of 10 evaluable patients, there were 9 PR and 1 SD. We conclude that cyclophosphamide at a dose of 2.0 g/m2/day x 2 days q 4 weeks in association with Sargramostim demonstrates marked activity with acceptable toxicity in patients with recurrent medulloblastoma.
 ...
PMID:Cyclophosphamide in combination with sargramostim for treatment of recurrent medulloblastoma. 762 28

We studied the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the suppression of hematopoiesis associated with the use of the antiviral drug zidovudine (AZT) administered in vivo to normal mice, as determined by measuring peripheral blood indices, and assays of hematopoietic progenitors, i.e. erythroid (CFU-E/BFU-E), myeloid (CFU-GM), and megakaryocyte (CFU-Meg) from bone marrow and spleen. Previous studies from this laboratory have established that dose-escalation zidovudine induced a dose-dependent decrease in hematocrit, WBC, and platelets with altered populations of bone marrow and splenic erythroid, myeloid and megakaryocyte progenitors when administered to normal mice. Daily administration of GM-CSF (10 micrograms/kg/bw) was associated with altered peripheral blood indices and progenitor cells. Dose-escalation AZT, i.e. 0.1, 1.0 and 2.5 mg/ml, was associated with a comparable reduction in all indices, i.e. hematocrit, WBC, and platelets during the 6-week examination period. GM-CSF reduced zidovudine-induced myeloid toxicity (concentration < 2.5 mg/ml) which was associated with an increase in bone marrow and splenic CFU-GM. High concentration, i.e. 2.5 mg/ml still produced myelosuppression irreversible with GM-CSF. GM-CSF induced a reduction in circulating platelets following zidovudine treatment at weeks 2 and 4 with the 1.0 mg/ml and 2.5 mg/ml treatment groups respectively, compared to a persistent decrease in platelets in the presence of zidovudine alone. GM-CSF BFU-E were elevated indicating the restriction in erythoid differentiation was still present. These studies demonstrate GM-CSF influences myeloid and megakaryocyte recovery, but not the erythoid suppression associated with the antiviral drug zidovudine.
 ...
PMID:Prevention of hematopoietic myeloid and megakaryocyte toxicity associated with zidovudine in vivo in mice with recombinant GM-CSF. 795 Sep 2

In recent years, biologic response modifiers, including recombinant cytokines and hematopoietic growth factors, have been used to treat patients with refractory hematologic malignancies and solid tumors, as well as chemotherapy-associated myelosuppression and thrombocytopenia and treatment- and/or malignancy-related anemia. Various cytokines appear to be effective in patients with hematologic malignancies, but long-term and durable responses in the salvage setting are rare. In patients with solid tumors, such as renal cell carcinoma, malignant melanoma, and colorectal cancer, cytokines may have a limited role in primary therapy but are of little value in salvage therapy. Complications of malignancy and antineoplastic therapy are widely treated with hematopoietic growth factors, like granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, and more recently the interferons and interleukins have demonstrated a potential role in this setting.
 ...
PMID:Biologic therapy in patients receiving salvage treatment. 809 Dec 47

Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.
 ...
PMID:rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU. 812 85

Despite 20 years of chemotherapy trials in advanced NSCLC, optimal regimens leading to complete remissions have not been identified. The decision to treat a patient who has inoperable advanced NSCLC must take into account the toxicity of the chemotherapy. The toxicities most often reported are myelosuppression and emesis; however, these trials were performed before the use of colony-stimulating factors (ie, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor) and serotonin antagonists (ie, ondansetron). Granulocyte colony-stimulating factor has been shown to shorten the duration of neutropenia and thus decrease the incidence of confirmed infections. Colony-stimulating factors also may allow significant escalation of the dose of chemotherapy. Ondansetron has been shown to ameliorate cisplatin-induced emesis better than other antiemetics. The performance status of a patient has been noted to be a predictor for survival, as well as response to therapy, and this should also be taken into consideration when deciding to treat a patient with advanced inoperable NSCLC. Ideally, patients with stage IV NSCLC should be placed on investigational therapy protocols to identify optimally active combinations of agents. One approach to the patient with inoperable NSCLC who is ineligible for a trial, or who does not wish to participate in a trial, is to offer chemotherapy soon after diagnosis, as patients in this category are likely to be less symptomatic and have optimal performance status. A platinum-containing regimen would seem to be the most reasonable regimen in such a patient. It is hoped that ongoing trials in suitable candidates will lead to the identification of more consistently active agents to deal with this devastating disease.
 ...
PMID:Chemotherapy outcomes in advanced non-small-cell lung carcinoma. 839 89

The effects of indomethacin administration on Pseudomonas aeruginosa infection were investigated in neutropenic mice. Cyclophosphamide-treated mice received the drug at 2.5 to 12 mg/kg according to different regimens, to be challenged with a lethal intraperitoneal inoculum of P. aeruginosa 5 days after myelosuppression. A single exposure of the neutropenic mice to 7 mg/kg indomethacin during the first 6 to 48 hr after myelosuppression was found to optimally restore the animals' antibacterial resistance, both in terms of survival of infected mice and clearance of the organisms from the peritoneal cavity. However, when administered 24 hr before challenge, the same drug dosage had no effect in enhancing survival. Cure was associated with accelerated hematopoietic recovery, as revealed by peripheral blood leukocyte counts, spleen weight and cellularity, cellular response to infection in the peritoneal cavity, and enumeration in vitro of bone marrow and splenic granulocyte-macrophage colony-forming cells. Following indomethacin administration, a rapid burst in the levels of colony-stimulating activity was detected in the bloodstream, and exposure of splenic macrophages or marrow cells to indomethacin in vitro was found to result in enhanced expression of transcripts specific for granulocyte-macrophage colony-stimulating factor. These data support the notion that the administration of cyclooxygenase inhibitors may be useful in promoting hematopoiesis and reducing the risk of opportunistic infections in myelosuppressed hosts.
 ...
PMID:Accelerated hematopoietic recovery and protective effect of the cyclooxygenase inhibitor indomethacin in bacterial infection of neutropenic mice. 845 76

We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.
 ...
PMID:The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group. 845 7

Patients with refractory malignant lymphoma (RML) have a poor prognosis when treated with conventional chemotherapy. The use of high-dose chemotherapy has been limited by secondary myelosuppression. We report the use of intensive and short-duration chemotherapy in patients with RML who received granulocyte-macrophage colony-stimulating factor (GM-CSF) instead of hematological support and salvage with bone marrow transplantation or infusion of peripheral blood stem cells. Thirty-one patients with RML were treated with cyclophosphamide: 7 g/m2, iv on day 1, followed by GM-CSF: 5 micrograms/kg/day, subcutaneously until hematological recovery (granulocytes > 1.8 x 10(9)/L) started on day 2. Methotrexate, 5 g/m2, was also given when the granulocytes and platelets counts were normal, followed by leucovorin rescue. Epirubicin, 180 mg/m2, iv, was given on day 29 if the granulocyte count was normal, and GM-CSF was started on day 30. Complete response was obtained in 21 out of 31 patients (67%) and partial response in 4 more, thus an overall response was achieved in 80% of the treated patients. Time to treatment failure was 24+ months, and the overall survival was 28+ months. Hematological toxicity grade IV, according to the WHO criteria was observed in all cycles, however hematological recovery was already evident on day 13 +/- 2. Eleven patients developed infection related to the treatment, but no therapy related death was observed. GM-CSF was well tolerated with minimal toxicity. Is evident that GM-CSF can act as hematological support after high-dose chemotherapy in patients who cannot undergo bone marrow transplantation programs.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:GM-CSF instead of hematological support during high-dose chemotherapy for refractory malignant lymphoma. 858 Aug 3

Endogenous plasma levels of granulocyte colony stimulating factor (G- CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF),IL-6 and IL-10 were measured in a total of 70 patients undergoing cytoreductive chemotherapy for treatment of acute leukaemia or non-Hodgkin's lymphomas. the diagnoses were acute myeloid leukaemia (AML; n = 30), acute lymphoblastic leukaemia (ALL;n=6), non-Hodgkin's lymphomas (NHL; n=11) and other malignant haematological disorders including myelodysplastic syndromes (n=23). After chemotherapy, plasma G-CSF was elevated (mean 5.6 ng/ml; range 1.2-10 ng/ml), and was inversely correlated with white blood cell counts (WBC) (r=-0.7, p<0.001). Occurrence of fever (T>38.0 degrees C) during severe myelosuppression (WBC<1x10(9)/1) was associated with an additional increase of G-CSF levels (P<0. (P<0.001). Plasma IL-6 correlated significantly with fever (range <1 to 1100 pg/ml, mean 130 pg/ml; r=0.5, P<0.001) but revealed only a weak association with WBC or platelet counts. In patients treated with recombinant G-CSF (n = 9), an association between IL-6 and fever was still observed after chemotherapy. During the nonfebrile status (total n = 242; AML n = 124), IL-6 levels remained <9 pg/ml in 90% of cases, whereas G-CSF increased with leucopenia (r = -0.72;P<0.001). In contrast, endogenous GM-CSF remained normal and IL-10 showed only a slight increase (21% of samples; maximum 22 pg/ml) in severe leucopenia. In particular, IL-10 levels did not correlate with G-CSF or IL-6 levels. We conclude that systemic release of G-CSF and IL-6 is obviously nit abrogated by cytoreductive chemotherapy in acute leukaemia and NHL may add to the therapeutic efficacy of recombinant cytokines. Also, plasma levels of G-, GM-CSF or IL-6 appear to be regulated by separate mechanisms.
 ...
PMID:Regulated plasma levels of colony-stimulating factors, interleukin-6 and interleukin-10 in patients with acute leukaemia and non-hodgkin's lymphoma undergoing cytoreductive chemotherapy. 861 84

High-grade non-Hodgkin's lymphomas (NHL) can potentially be cured with combination chemotherapy, although the optimum schedules still have to be defined. Clinical trials with intensive chemotherapy are predominantly limited by myelosuppression. Here, haematopoetic growth factors open up the possibility of reducing chemotherapy-associated toxicities. In this randomised pilot study, we investigated the effects of a recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) following combined chemotherapy with vincristine, doxorubicin, cyclophosphamide, prednisone and etoposide (VACPE). A total of 35 patients with high-grade NHLs were randomised to receive either rhGM-CSF or placebo during the first two chemotherapy cycles and rhGM-CSF for all following cycles. rhGM-CSF was administered at a dosage of 5 micrograms/kg for 10 days or until neutrophils were > 1/nl following chemotherapy. The analyses revealed a significant reduction of neutropenia and duration of neutropenia in the rhGM-CSF group. Adverse events were rare and generally mild apart from one anaphylactoid reaction. No effects of rhGM-CSF were observed concerning the platelet nadir or duration of thrombocytopenia. The benefit of rhGM-CSF for response induction and survival via rhGM-CSF-supported dose intensification remains to be determined.
 ...
PMID:Recombinant human granulocyte-macrophage colony-stimulating factor after combined chemotherapy in high-grade non-Hodgkin's lymphoma--a randomised pilot study. 865 36


<< Previous 1 2 3 4 5 6 7 8 Next >>