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)

Colony-stimulating factors (CSFs) shorten the duration of myelosuppression following chemotherapy and, thus, allow the administration of higher doses. This study evaluates the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in allowing administration of high-dose cyclophosphamide in combination with doxorubicin. Ninety women with metastatic, locally advanced, or high-risk (> or = 10 positive nodes) breast cancer and no prior anthracycline treatment were given doxorubicin (60 mg/m2) with progressively increased doses of cyclophosphamide (1,200 mg/m2, 1,800 mg/m2, and 2,400 mg/m2). The first 60 patients received GM-CSF; the remaining 30, G-CSF. The maximum tolerated dose was not reached with 2,400 mg/m2 of cyclophosphamide. When compared to GM-CSF, G-CSF significantly reduced the duration of granulocytopenia (P < .001). No differences in duration of thrombocytopenia were noted. The results were not sufficiently consistent to indicate a trend toward reduction in rates of febrile neutropenia with one CSF versus the other. However, patients who received G-CSF were hospitalized less frequently than those receiving GM-CSF. With CSFs, high-dose cyclophosphamide in combination with doxorubicin can be safely administered on an outpatient basis. A shorter duration of granulocytopenia resulted from the use of G-CSF than from GM-CSF.
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PMID:The efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte macrophage colony-stimulating factor in permitting the administration of higher doses of cyclophosphamide in a doxorubicin-cyclophosphamide combination. An NSABP pilot study in patients with metastatic or high-risk primary breast cancer. National Surgical Adjuvant Breast and Bowel Project. 752 93

We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.
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PMID:High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities, and hematopoietic recovery after autologous stem cell reinfusion. 752 92

Cumulative thrombocytopenia is a dose-limiting toxicity of dose-intensive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to each cytokine administered alone. Ninety-three patients with advanced breast cancer were treated with five cycles of FLAC chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg) administered subcutaneously for each schedule of cytokine administration. The GM-CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM-CSF (schedule B) was associated with higher platelet nadirs, shorter durations of platelet counts less than 50,000/microL, and the need for fewer platelet transfusions over five cycles of FLAC chemotherapy compared with concurrent cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated with unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared with each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF with IL-3 administered for 9 days before beginning GM-CSF may be superior to shorter durations of IL-3 administered sequentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematologic toxicity associated with multiple cycles of FLAC chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted.
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PMID:A phase I study of sequential versus concurrent interleukin-3 and granulocyte-macrophage colony-stimulating factor in advanced breast cancer patients treated with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy. 757 83

The application of recombinant colony stimulating factors for chemotherapy induced granulocytopenia is becoming common in clinical oncology. Here we report on localized cutaneous side effects after subcutaneous administration of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) in 11 patients with breast cancer receiving cytostatic treatment. Seven patients suffering from inflammatory breast cancer received cytostatic chemotherapy with mitoxantrone/cyclophosphamide, whereas four patients suffering from noninflammatory breast cancer received high-dose epirubicin/cyclophosphamide, respectively. rh GM-CSF was applicated subcutaneously in a dose of 5 micrograms/kg/d for at least ten days. In all patients, sharply demarked, maculous itching and burning erythemas restricted to the injection sites occurred after three to four injections of rh GM-CSF. These eruptions cleared within 2 to 3 weeks, but reappeared after reexposure to rh GM-CSF. In contrast to previous sporadic reports, no generalized erythemas were observed. Because of this unexpected and subjectively intolerable side effect, rh GM-CSF administration had to be interrupted in all patients. Histopathological findings revealed skin infiltration with lymphocytes, monocytes/macrophages, neutrophils, and occasionally eosinophils, respectively. Since GM-CSF is known to alter immune functions, it seems likely that the eruptions were at least in part due to local immune reactions.
Breast Cancer Res Treat 1995 Jun
PMID:Cutaneous side effects in breast cancer patients treated with cytostatic polychemotherapy and rh GM-CSF: immune phenomena or drug toxicity? 757 85

Studies on circulating human mononuclear cells and rodents have suggested that cytokines such as interleukin-1 (IL-1) and IL-6 may be paracrine mediators of postmenopausal bone loss. However, the assumption that the concentration of these cytokines is increased in the local bone microenvironment of postmenopausal women is still unproved. To address this question, we aspirated bone marrow from the iliac crest of 40 women during surgery for localized breast cancer and analyzed cytokine release in short term cultures. Cytokine levels in the cell supernatants from premenopausal (n = 12) and late postmenopausal (n = 18) subjects were not significantly different. Bone marrow cells from women who had discontinued estrogen replacement within 1 month before aspiration (n = 5) secreted significantly more IL-1 alpha, tumor necrosis factor-alpha, IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor than bone marrow cells from either premenopausal or late postmenopausal subjects. Increased levels of IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor were also observed in cultures from women who were within 5 yr of natural menopause (n = 5). Our data show that estrogen withdrawal is associated with an increased potential of human bone marrow cells to release bone-resorbing cytokines and strengthen the hypothesis that these cytokines may play a role in the accelerated bone resorption after menopause.
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PMID:Increased cytokine secretion by human bone marrow cells after menopause or discontinuation of estrogen replacement. 759 50

Peripheral blood progenitor cells (PBPCs) were collected without prior association with chemotherapy but after the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) produced in Chinese hamster ovary cells (CHO-GM, regramostim), Escherichia coli (E. coli-GM, molgramostim), or yeast (Yeast-GM, sargramostim) and used in conjunction with autologous bone marrow after high-dose chemotherapy in 69 patients with breast cancer or melanoma. The mean peripheral white blood cell (WBC) counts increased by 2.2 to 2.7-fold after regramostim, 4.5 to 7.3-fold after molgramostim and 4.3-fold after sargramostim. All patients underwent three leukaphereses. The mean (+/- standard error) total nucleated pheresed cells per kg x 10(8) were 4.15 +/- 0.56, 15.10 +/- 1.77 and 7.24 +/- 1.00 for patients receiving regramostim, molgramostim or sargramostim respectively. The mean (+/- standard error) granulocyte-macrophage colony-forming units per kg x 10(4) mobilized into the PB were 8.75 +/- 3.63, 71.03 +/- 17.85, and 65.11 +/- 18.74 for patients receiving regramostim, molgramostim, or sargramostim respectively. The total mean (+/- standard error) CD34+ cells per kg x 10(7) collected by three leukaphereses were 3.28 +/- 1.62, 1.34 +/- 0.51 and 2.57 +/- 1.93, for patients receiving regramostim, molgramostim or sargramostim respectively. The use of either molgramostim- or sargramostim-primed PBPCs led to complete elimination of absolute leukopenia with a WBC count under 100/mm3 in 64% and 77% of patients treated, respectively. Patients receiving molgramostim-primed PBPCs required fewer red blood cells transfusions than patients receiving regramostim-primed PBPCs (p = 0.0062). Our data indicate that PBPCs collected without prior association with chemotherapy but after either molgramostim or sargramostim with autologous bone marrow support and GM-CSF shorten the hematopoietic recovery after myeloablative chemotherapy in patients with breast cancer or melanoma.
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PMID:Effects of granulocyte-macrophage colony stimulating factor produced in Chinese hamster ovary cells (regramostim), Escherichia coli (molgramostim) and yeast (sargramostim) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy. 749 86

The effect of priming on occult tumor cell involvement of peripheral blood (PB) and PB progenitor cell (PBPC) collections is poorly characterized. Using sensitive immunocytochemistry (ICC) and tumor clonogenic assays (TCA) specific for epithelial-derived tumor cells, hematopoietic specimens were analyzed for PBPC and occult tumor cell involvement in 28 patients with chemotherapy-sensitive stage IIIB or IV breast cancer. Before PBPC priming, tumor was detected by ICC in PB of 1 of 23 (4%) patients and in bone marrow (BM) harvests of 4 of 27 (15%) patients. Fifteen days after cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF) priming, 2 of 28 (7%) patients had ICC-positive PBPC collections. The median amplification of CD34+ PBPC during this time was over 19-fold (range, < 1 to 199). One patient had pretreatment tumor involvement of both PB and BM. One patient grew tumor colonies in TCA; the PB and BM were ICC- and TCA-positive, but the PBPC collection was ICC-positive and TCA-negative. After cytoreduction with conventional-dose chemotherapy, patients with advanced breast cancer and histologically negative BM biopsy specimens have rare tumor cell involvement of PB and BM. Despite effective PBPC priming with cyclophosphamide and GM-CSF, clonogenic breast cancer cells were not found in the PBPC collection performed on day 15.
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PMID:Absence of breast cancer cells in a single-day peripheral blood progenitor cell collection after priming with cyclophosphamide and granulocyte-macrophage colony-stimulating factor. 784 2

The occurrence of arterial thrombosis reported in other breast cancer series has largely been confined to the upper extremities, ipsilateral to a previous mastectomy site and clinically manifest as cerebral vascular accidents. This case report describes 2 patients who experienced iliac artery thrombosis temporally related to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) and dose-intensive chemotherapy for metastatic breast cancer. A review of the literature concerning arterial thrombosis as relevant to breast cancer treatment and GM-CSF is included.
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PMID:Arterial thrombosis associated with granulocyte-macrophage colony-stimulating factor (GM-CSF) administration in breast cancer patients treated with dose-intensive chemotherapy: a report of two cases. 787 73

Following local treatment and doxorubicin-containing standard chemotherapy, 42 patients with surgical Stage II or IIIA breast cancer containing ten or more involved axillary nodes and 13 patients with Stage IIIB disease were treated with high-dose chemotherapy (TMJ) consisting of thiotepa (750 mg/m2), mitoxantrone (40 mg/m2), and carboplatin (1000 mg/m2), with autologous bone marrow (ABM) and peripheral stem cell (PSC) transplant, followed by irradiation and/or hormone therapy. Sargramostim (GM-CSF) support was given to most patients. The median time to transfusion independence was two weeks. Severe non-hematologic toxicity was uncommon, with no intensive care admission or treatment-related death. At a median follow-up of 17 months, eight patients have relapsed and five have died of tumor progression. No statement can yet be made regarding adjuvant efficacy, but this high-dose regimen is very well tolerated.
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PMID:TMJ: a well-tolerated high-dose regimen for the adjuvant chemotherapy of high risk breast cancer. 799 67

High-dose chemotherapy regimens can cure a number of otherwise incurable diseases, such as Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, acute leukemia (in remission), and breast cancer. Trials of high-dose chemotherapy have generally used autologous bone marrow transplant or peripheral blood stem cell support to ensure hematologic recovery after intensive chemotherapy and/or radiation. This report describes an approach in which high-dose carboplatin chemotherapy was followed initially by granulocyte-macrophage colony-stimulating factor (GM-CSF; Escherichia coli. Sandoz-Schering, East Hanover and Kenilworth, NJ) and in subsequent patients, by both GM-CSF and repeated cycles of peripheral blood progenitor cell (PBPC) collection and administration. The addition of PBPC to this regimen led to significant reductions in the duration of neutropenia and thrombocytopenia, the requirement for erythrocyte and platelet transfusions, the length of hospital stay, and the use of intravenous antibiotics in this group relative to those patients who received GM-CSF alone. In addition, laboratory studies are presented that show a direct correlation between the number of progenitor cells reinfused and the duration of neutropenia and thrombocytopenia. The report also reviews data indicating that circulating progenitor cells are depleted by this approach. This suggests that the number of progenitor cells available for mobilization is finite. Finally, the magnitude of these effects, and their implications for future trials with repetitive cycles of dose-intensive therapy, are discussed.
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PMID:High-dose carboplatin chemotherapy with GM-CSF and peripheral blood progenitor cell support: a model for delivering repeated cycles of dose-intensive therapy. 810 54


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