Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

No published data are available concerning the activity and tolerability of intramuscularly administered granulocyte colony-stimulating factor (G-CSF) in humans. To fill this gap, 19 patients with advanced ovarian cancer previously treated with at least one first-line chemotherapy cycle received the following myelosuppressive regimen: mitoxantrone (DHAD) 12 mg m-2 i.v. on day 1; ifosfamide (IFO) 4 g m-2 i.v. on days 1 and 2; mesna 800 mg m-2 i.v. t.i.d. on days 1 and 2. G-CSF (Filgrastim) was given at a dose of 5 micrograms/kg/day i.m. from day 6 to day 19, its pharmacokinetics being assessed in five patients. The neutrophil nadir was observed after a mean period of 8 days, and the neutrophil count was < 1.0 x 10(3) mm-3 for a mean of 6 days during the cycle of chemotherapy. The neutrophil count fell after the withdrawal of G-CSF on the 19th day of treatment. The difference in absolute neutrophil count between day 19 and day 21 was statistically significant (P = 0.0001); nevertheless, at day 21 no WHO grade 3-4 neutropenia was reported. DHAD and IFO were respectively given at 95% and 93% of the planned dose. The pharmacokinetics of G-CSF i.m. seems to be similar to that of the drug given subcutaneously. No evidence of cumulative myelosuppression was observed. G-CSF was well tolerated and no complications were observed at the injection sites. In conclusion, if the results obtained in this pilot study regarding the activity of i.m. G-CSF are confirmed by a randomised trial, the intramuscular administration of G-CSF could become a valid alternative for patients who dislike the subcutaneous route and who are being treated with chemotherapy that does not induce profound thrombocytopenia.
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PMID:The intramuscular administration of granulocyte colony-stimulating factor as an adjunct to chemotherapy in pretreated ovarian cancer patients: an Italian Trials in Medical Oncology (ITMO) Group pilot study. 751 30

The haematopoietic growth factors interleukin-3 (IL-3), erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF, Neupogen) and granulocyte macrophage colony-stimulating factor (GM-CSF) are highly effective endogenous regulators of blood cell proliferation and differentiation. The results of initial clinical studies with these substances show a stimulation of haematopoiesis for numerous dysfunctions of the bone marrow, whereby the therapy of cytostatic-induced myelosuppression is of particular significance for the gynaecologist, specializing in oncology. After further experience with the individual substances, future development in this field will probably focus on the combined use of these growth factors, to stimulate all early developmental stages of haematopoiesis in the bone marrow and--in view of the line-specific effect--to achieve an effect on several lines of differentiation. Of the cytokines quoted, G-CSF (Neupogen) is so far the only growth factor, which is available for oncological indications. The approval of GM-CSF, IL-3 and EPO for oncological indications is pending. If the currently available results are confirmed by further clinical studies, it will be possible--over and above the improvement of cytostatic tolerance--to raise the current cytostatic doses limited by myelodepression, and to analyse, whether better oncological results can be achieved by more intensive chemotherapy, shorter application intervals, or by using previously impossible cytostatic combinations. The employment of haematopoietic growth factors could, in this way, lead to new oncological therapy concepts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New oncologic therapeutic approaches with hematopoietic growth factors]. 849 64

We report on our experience with the application of recombinant human granulocyte colony-stimulating factor (G-CSF, Neupogen, Hoffmann La Roche) in patients with various types of hematological malignancies, who had chemotherapy-induced myelosuppression, and in patients with idiopathic aplastic anemia. The administration of G-CSF was associated with marked increase in white blood cells counts (WBC) in twelve out of 14 treated patients. In one patient with aplastic anemia the WBC decreased rapidly to the initial value after the cessation of cytokine therapy. Significant increase of platelet number was observed in 6 patients. No toxicity was encountered with the hematopoietic growth factor therapy. Our study points to the fact that G-CSF have a stimulating effect on the regeneration of hematopoiesis, particularly within the granulopoietic compartment. The effect can be obtained both in a case of idiopathic- and cytostatic-dependent marrow aplasia.
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PMID:Treatment of chemotherapy-induced or idiopathic bone marrow aplasia with granulocyte colony-stimulating factor (G-CSF). 857 3

We report on an 66-year old female in whom we diagnosed uterine carcinosarcoma and concurrent breast cancer. As first-line treatment the patient received ifosfamide 4.8 mg/m2 body surface. During her second course of chemotherapy she developed sequentially life-threatening toxicities; severe emesis followed by nephrotoxicity, neurotoxicity and myelosuppression. Early prophylactic administration of rhG-CSF (Filgrastim) helped to overcome severe, potentially fatal myelosuppression. The course of severe toxicities following high doses of ifosfamide might reflect a dependent sequence, where one organ failure causes a subsequent organ failure. Prophylactic treatment of anticipated toxicity should be considered for the management of severe ifosfamide-induced toxicity. Such treatment may consist of sufficient antiemesis, sufficient hydration, as well as a therapy with methylene blue in case of severe neurotoxicity.
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PMID:[Sequential course and prospective management of ifosfamide-induced multi-organ toxicity]. 903 65

Paclitaxel is active in metastatic breast cancer. Combination studies have demonstrated complex interactions between paclitaxel and other cytotoxic agents, including sequence-dependent cytotoxic, toxicological, and pharmacological effects. The principal objectives of this study were to determine the maximum tolerated doses of paclitaxel (3-h infusion) and cyclophosphamide (1-h infusion) administered every 3 weeks with granulocyte colony-stimulating factor (Filgrastim) and to determine if the sequence-dependent toxicological effects that have previously been observed with this combination when paclitaxel was administered over 24 h were evident when paclitaxel was administered over 3 h. Fifteen women with metastatic breast cancer were treated. Starting doses were 200 mg/m2 paclitaxel and 1600 mg/m2 cyclophosphamide, with granulocyte colony-stimulating factor (5 micrograms/kg/day) given s.c. beginning 24 h after chemotherapy. Doses of both drugs were escalated in cohorts of at least four patients. The sequence of drug administration was alternated with each consecutive patient and with each subsequent course of therapy in each individual patient, enabling the evaluation of sequence-dependent toxicological and pharmacological effects. Severe myelosuppression was the principal dose-limiting toxicity for this regimen, precluding dose escalation above 200 mg/m2 paclitaxel and 1600 mg/m2 cyclophosphamide, the maximum tolerated dose for this combination on this schedule. As has been previously demonstrated with this combination, when paclitaxel is administered over 24 h, the hematopoietic toxicity was sequence dependent. Paired analysis of toxicity data using each patient as her own control indicated more severe hematological toxicity in courses in which paclitaxel was administered first. There was no evidence of sequence-dependent effects on the pharmacokinetics of these drugs that might account for this phenomenon. The impact of drug sequencing on toxicity should be considered in the further development of combination therapy containing alkylating agents and paclitaxel, when the latter is administered over 3 h.
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PMID:Sequence-dependent hematological toxicity associated with the 3-hour paclitaxel/cyclophosphamide doublet. 951 22

Megakaryocyte growth and development factor (MGDF) stimulates megakaryopoiesis and thrombopoiesis in vivo. Previous studies indicate that administration of pegylated recombinant human (PEG-rHu) MGDF in combination with recombinant murine granulocyte colony-stimulating factor (rMuG-CSF) prevented lethality and reduced hematotoxicity in carboplatin-treated/irradiated mice, a disease-state animal model of radio-chemotherapy. In the current study we have further characterized the effects of PEG-rHuMGDF in combination with rMuG-CSF with respect to clinical chemistry, hematology variables, and histologic evaluations to determine whether any potential toxicological interaction exists both in normal and myelosuppressed mice. Myelosuppression and subsequent thrombocytopenia in mice was induced with a combination of a single intraperitoneal injection of 1.25 mg carboplatin followed 4 h later with sublethal gamma irradiation exposure of 500 rad. Both normal and carboplatin-treated/irradiated mice were administered daily subcutaneous injections of 50 micrograms/kg PEG-rHuMGDF alone and in combination with 10 micrograms/kg rMuG-CSF for 21 consecutive days. Administration of PEG-rHuMGDF alone or in combination with rMuG-CSF to carboplatin-treated/irradiated mice increased survival 70 and 100%, respectively, and accelerated platelet recovery. Microscopic examination of nonhematopoietic organs showed no evidence of any morphological changes in normal and carboplatin-treated/irradiated animals. In hematopoietic organs clinically significantly increased granulopoiesis and megakaryopoiesis, as well as extramedullary granulopoiesis within the mandibular and mesenteric lymph nodes, were present. The erythroid line was unaffected by cytokine treatment. In normal, non-carboplatin-treated/irradiated mice, platelet counts increased 6 and 12-fold above baseline in the groups administered PEG-rHuMGDF alone or in combination with rMuG-CSF, respectively. The results of this study provide a basis for coadministration of PEG-rHuMGDF with Filgrastim (rHuG-CSF) in the clinical treatment of myelosuppression induced by radiation and chemotherapy.
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PMID:Systemic effects of pegylated recombinant human megakaryocyte growth and development factor in combination with recombinant murine granulocyte colony-stimulating factor in a murine model of myelosuppression. 984 14

Administration of combination chemotherapy to children with metastatic neuroblastoma induces profound myelosuppression resulting in chemotherapy treatment delays and febrile neutropenic episodes. The objective of this randomised multicentre study was to assess the incidence, duration and severity of neutropenia when filgrastim is added to induction chemotherapy administered to patients with metastatic neuroblastoma. In this study, 59 patients with metastatic neuroblastoma were randomised to receive chemotherapy (control group, n = 28) or chemotherapy plus filgrastim (filgrastim group, n = 31). Chemotherapy consisted of four cycles of cyclophosphamide, vincristine and doxorubicin (CADO) alternating at 21-day intervals with cisplatin and etoposide (CDDP-VP16). Filgrastim was administered subcutaneously at a dose of 5 micrograms/kg/day from day 7 for up to 14 days. The incidence of neutropenia (absolute neutrophil count [ANC] < 0.5 x 10(9)/l) in the filgrastim group was not reduced after the first CADO course. However, significant reductions were observed after courses 2, 3 and 4. The duration of neutropenia and of intravenous antibiotic use were significantly reduced in the filgrastim group over the whole study period (9 days versus 26 days, P < 0.001; 12 days versus 20 days, P = 0.04, respectively). However, the duration of hospitalisation and the incidence of febrile neutropenia were not significantly reduced. Compliance to treatment was good and the ability to administer chemotherapy without treatment delays was significantly better in the filgrastim group (P < 0.05). Event-free survival was greater in the filgrastim than in the control group (2.4 years versus 1.3 years; P = 0.072). Filgrastim is a beneficial adjunct to combination induction chemotherapy used in the treatment of metastatic neuroblastoma.
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PMID:An open-label, multicentre, randomised phase 2 study of recombinant human granulocyte colony-stimulating factor (filgrastim) as an adjunct to combination chemotherapy in paediatric patients with metastatic neuroblastoma. 984 55

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

Chemotherapy-induced myelosuppression is the most common dose-limiting side effect of cancer chemotherapy. Neutropenia is a serious risk with chemotherapy, associated with infectious complications, use of intravenous antibiotics, hospitalization, and even death. The occurrence of febrile neutropenia can lead to dose reductions and delay in subsequent cycles of chemotherapy that may have a detrimental affect on overall survival and disease-free survival. Granulocyte colony-stimulating factors (G-CSF) can reduce the duration of severe neutropenia, the incidence of febrile neutropenia, and allow planned dosing and timing of chemotherapy. Filgrastim is a G-CSF that has demonstrated benefit for the treatment and prophylaxis of chemotherapy-induced neutropenia (CIN), but its short half-life requires repeated daily subcutaneous injection. Pegfilgrastim is a recombinant G-CSF created by attaching a polyethylene glycol (PEG) molecule to the filgrastim protein. Once-per-cycle dosing of pegfilgrastim has been evaluated in clinical trials using myelosuppressive chemotherapy in breast cancer, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Trials have demonstrated that pegfilgrastim is comparable in safety and efficacy to filgrastim for decreasing the duration of severe neutropenia after chemotherapy in patients with nonmyeloid malignancy. This review will summarize recent clinical trial results and novel uses of pegfilgrastim.
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PMID:Pegfilgrastim use during chemotherapy: current and future applications. 1549 75

Anthracycline- and taxane-based adjuvant chemotherapy regimens have become the most commonly used regimens in the United States for high-risk, early-stage breast cancer. Growth factor support is an essential component of therapy for several of the most commonly used adjuvant chemotherapy regimens that frequently cause substantial myelosuppression and anemia. Extensive data now exist to demonstrate the efficacy of both long- and short-acting myeloid growth factors in patients receiving dose-dense AC --> paclitaxel. This article will explore prophylactic use of both filgrastim (Neupogen) and pegfilgrastim (Neulasta) in recent clinical trials.
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PMID:Myeloid growth factor support for dose-dense adjuvant chemotherapy for breast cancer. 1737 Sep 24


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