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)

This phase I randomized study was designed in order to verify if the sequential administration of filgrastim, a granulocyte colony-stimulating factor (G-CSF), and molgramostim, a granulocyte-macrophage colony-stimulating factor (GM-CSF), was superior to filgrastim alone in improving tolerance of dose-intensified carboplatin (CBDCA), cyclophosphamide (CTX), and etoposide (VP-16). A group of 10 heavily pretreated patients with stage IV disease and no therapeutic option were enrolled into the study. They received two courses of the same chemotherapy with CTX and VP-16 at doses of 1,500 mg/m2 and 400 mg/m2, respectively. CBDCA doses were escalated from 450 to 600 mg/m2. After chemotherapy each patient was allocated randomly to receive either 14 days of G-CSF (arm A) or 7 days of G-CSF followed by 7 days of GM-CSF (arm B). Crossover in the second chemotherapy course was accomplished. Both G-CSF and GM-CSF were given 5 microg/kg/day, subcutaneously. Twenty chemotherapy courses are evaluable, 10 in each arm. Absolute neutrophil count < 1 x 10(3)/microl was observed for 54 days in arm A vs. 68 days in arm B (P < 0.02); platelet (PLT) count < 20 x 10(3)/microl, 57 days vs. 30 days (P < 0.01); days of hospitalization 35 vs. 16 (P < 0.38); PLT transfusion, 107 vs. 58 (P < 0.01); packed red blood cell unit transfusions, 15 vs. 5 (P < 0.13). Seven patients had responses. These data indicate that dose-intensified chemotherapy may be delivered without bone marrow or peripheral stem cell support, with acceptable toxicity, and that, while G-CSF alone shortens days of neutropenia, the combination of the two cytokines shortens the time of thrombocytopenia and decreases the number of PLT transfusions.
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PMID:Randomized trial of filgrastim vs. sequential filgrastim and molgramostim after dose-intensified carboplatin, cyclophosphamide, and etoposide: a phase I pilot study. 912 2

Cyclophosphamide is an alkylating agent that has shown activity in the treatment of pediatric brain tumors, including high-grade gliomas. This study was designed to evaluate the response of patients with newly diagnosed glioblastoma multiforme to pre-radiotherapy cyclophosphamide. Fourteen patients with glioblastoma multiforme were treated with high-dose cyclophosphamide (2 g/m2/day for 2 doses every 28 days) followed by either sargramostim or filgrastin. Sargramostim was given 250 microg/m2 subcutaneously twice a day continuing through the leukocyte nadir until the absolute neutrophil count was more than 1000 cells/microl for 2 consecutive days. The filgrastin dose was 10 microg/kg given subcutaneously once daily until the post nadir absolute neutrophil count was > or = 10,000 cells/microl. A total of 46 courses was given. Four patients received a total of 3 courses, 7 patients completed 4 courses and 3 patients received 2 courses. Three patients demonstrated complete response; 3 stable disease; and 8 progressive disease. The most common toxicity was hematologic, requiring platelet and packed red blood cell transfusions, with 13 admissions for neutropenia with fever. There were no deaths related to infection or bleeding. These results suggest that high-dose cyclophosphamide has modest activity with acceptable toxicity against newly diagnosed glioblastoma multiforme.
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PMID:Evaluation of pre-radiotherapy cyclophosphamide in patients with newly diagnosed glioblastoma multiforme. Writing Committee for The Brain Tumor Center at Duke. 1089 68

Cyclophosphamide is an alkylating antineoplastic agent used in several conditions. However, little is known about the mechanism of its pulmonary toxicity. In the present study, we determined that human lung fibroblasts release activity for neutrophils and monocytes in response to cyclophosphamide in a dose- and time-dependent manner. Checkerboard analysis revealed that both neutrophil and monocyte activities were chemotactic. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular-sieve column chromatography revealed that both neutrophil (NCA) and monocyte (MCA) chemotactic activities had multiple peaks. NCA was inhibited by a leukotriene B(4) receptor antagonist and anti-interleukin-8 and anti-granulocyte colony-stimulating factor antibodies. MCA was attenuated by a leukotriene B(4) receptor antagonist and anti-monocyte chemoattractant protein-1 and anti-granulocyte-macrophage colony-stimulating factor antibodies. The concentrations of interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor significantly increased in response to cyclophosphamide. These data suggest that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing NCA and MCA in response to cyclophosphamide.
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PMID:Cyclophosphamide stimulates lung fibroblasts to release neutrophil and monocyte chemoattractants. 1135 Jul 99

Cyclophosphamide, interferon-alpha and betamethasone are all effective agents for the treatment of multiple myeloma (MM) with different mechanisms of action. The clinical effect of a combination of cyclophosphamide 725 mg/m(2) i.v. days 1 and 3, interferon-alpha 7 x 10(6) IE/m(2) s.c./day, days 1-4 and betamethasone 30 mg orally days 1-4 (CIB) was studied in patients aged 60-75 years with previously untreated MM stages II and III. Granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 microg/kg/day s.c. was administered to all patients from day 5 until the day the granulocyte count exceeded 1.0 x 10(9)/l. CIB was repeated every fourth week. Interferon-alpha 3 x 10(6) IE s.c. t.i.w. was given as maintenance therapy in responding patients.A total of 28 patients (median age: 67 years) entered the study. In all, 12 patients had stage II and 16 had stage III MM. A total of 22 patients (79%) showed an objective response, including five complete remissions (CR) and 17 partial remissions (PR). All seven patients with Bence-Jones MM responded (five CR and two PR). The median response duration time was 14 months (range 5-38+). CIB was relatively well tolerated although febrile neutropenia or septicaemia occurred in 5% of the cycles and a dose-reduction of cyclophosphamide due to grade IV neutropenia was performed in 11% of the patients.CIB seems to be an effective regimen for remission induction in MM patients aged up to 75 years as an alternative to VAD (vincristine, doxorubicin, dexamethasone) if a regimen with intensity higher than that of oral melphalan/prednisone is warranted.
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PMID:Phase II study of cyclophosphamide, interferon-alpha and betamethasone (CIB) as induction therapy for patients 60-75 years of age with multiple myeloma stages II and III. 1287 49

The biological mechanisms by which the association of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is expected to effectively reduce the hematological toxicity associated with chemotherapy (CT) are not completely elucidated. We exploited the cell kinetic changes of the bone marrow CD34(+) cell subset after CT followed by the IL-3+GM-CSF together with the clinical effects of this association. Eighteen patients with advanced cancers and normal hematopoiesis were treated with an intensified CT course (mg/m(2): CTX 1100, epirubicin 100, VP-16 200; iv day 1). Six cycles were planned at 14-day intervals with the support of IL-3 (5 mu g/kg/day; from day 2 to 6) sequenced with GM-CSF (same dose; from day 7 to 11). DNA content and bromodeoxyuridine incorporation were evaluated using flow cytometry on immunomagnetically-sorted bone marrow CD34(+) cells, at baseline and at different times (days 5, 6, 7, 8, 11 and 14) after CT followed by IL-3+GM-CSF. Treatment with IL-3 induced a marked increase in the % of myeloid precursors with respect to the baseline and in the % of CD34(+) cells in S-phase. However, while the first parameter remained elevated until day 14, the enhanced proliferative activity of the CD34(+) cell subset decreased after IL-3 was stopped and remained significantly low during GM-CSF administration. These data suggest a negative rebound effect on CD34(+) cell proliferation after IL-3 discontinuation which is maintained during GMCSF, that led to kinetic refractoriness of the hyperplastic marrow. In the 99 courses completed a rapid neutrophil and platelet recovery was obtained without cumulative multilineage toxicity. The modifications of CD34(+) cell cycling after CT followed by IL-3+GM-CSF could provide additional myeloprotection during multicyclic, dose-intensive programs.
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PMID:Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy in patients with solid tumors. 2154 3

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted.
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PMID:A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer. 2511 55

The aim of this study is to investigate the protective effects of a small molecular fraction (SMF) of Polygoni multiflori Radix Praeparata (PMRP) in a cyclophosphamide (CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay (ELISA); The level of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase (GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.
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PMID:Hematopoietic effect of small molecular fraction of Polygoni multiflori Radix Praeparata in cyclophosphamide-induced anemia mice. 3151 85


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