Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin-cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose-limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.
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PMID:Effects of interleukin-3 after chemotherapy for advanced ovarian cancer. 151 36

Nine patients with bone marrow failure and prolonged severe cytopenias were treated with recombinant human interleukin-3 (rhIL-3) at doses ranging from 30 micrograms/m2 to 500 micrograms/m2. rhIL-3 was administered in a subcutaneous bolus injection daily for 15 days. Platelet counts increased by a mean of 6-fold (range: 1.3- to 14.3-fold) in five out of eight evaluable patients. Reticulocyte counts increased 2.9-fold in three patients, and neutrophil counts increased by a mean of 3.1-fold in all eight patients. Platelet transfusions could be discontinued after treatment with rhIL-3 in two out of three evaluable transfusion-dependent patients. Only mild side effects, mainly fever and headache, were observed. These results indicate that rhIL-3 functions as a multilineage hematopoietic growth factor in vivo in patients with secondary bone marrow failure.
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PMID:Recombinant human interleukin-3 in patients with hematopoietic failure. 185 56

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.
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PMID:Biologic effects of recombinant human interleukin-3 in vivo. 196 May 53

Interleukin-3 (IL-3) is a T-cell-derived colony-stimulating factor (CSF) whose primary targets include relatively early, multipotential, hematopoietic progenitor cells. In this trial, we treated 24 patients with recombinant human IL-3 given by a daily 4-hour intravenous infusion for 28 days. The dose levels were 30, 60, 125, 250, 500, 750, and 1,000 micrograms/m2/d. At least three patients were entered at every dose level. Each participant suffered from bone marrow failure, with the underlying diagnosis being myelodysplastic syndrome (13 patients), aplastic anemia (eight patients), or aplasia after prolonged high-dose chemotherapy (three patients) for multiple myeloma, breast cancer, or acute myelogenous leukemia. Most patients tolerated therapy well, with the most frequent side effects being low-grade fever and headaches. Hematopoietic changes included modest increases in neutrophil counts (eight patients), eosinophil counts (six patients), platelet counts (three patients), and reticulocyte counts (two patients). An increase in blasts occurred in one patient who had refractory anemia with excess blasts in transformation and was reversible once IL-3 was discontinued. In addition, one patient with chronic myelomonocytic leukemia showed an increase in monocytes (and granulocytes). Progression to acute leukemia did not occur. Pharmacokinetic analyses showed a rapid clearance with a mean half-life of 18.8 minutes at the 60 micrograms/m2/d dose, and 52.9 minutes at the 250 micrograms/m2/d dose. Serum concentrations of 10 to 20 ng/mL of IL-3 were achievable at the 250 micrograms/m2/d dose. Our observations indicate that recombinant human IL-3 can be given safely at doses of 1,000 micrograms/m2/d or less. In addition, on the basis of preclinical data and the biologic activity observed in this study, further trials of this molecule, alone and in combination with other growth factors, are warranted in patients with pancytopenia.
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PMID:Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. 204 65

Interleukin-3 (IL-3) is a glycoprotein belonging to the hematopoietic growth factor family that in preclinical in vitro and in vivo studies has exhibited a multilineage activity. Phase I/II trials with recombinant human IL-3 (rhIL-3) expressed in yeast are being done in patients with advanced malignancies as well as in patients with bone marrow failure states. Subcutaneous administration of rhIL-3 at dosages between 30 and 500 micrograms/m2 for 15 consecutive days has resulted in a dose-dependent increase in platelet counts as well as in a substantial increase in the number of circulating neutrophils, eosinophils, monocytes, and lymphocytes in patients with advanced malignancies but normal hematopoiesis. Erythropoiesis is less stimulated with an increase in hemoglobin concentration only in a minority of patients. In patients with secondary hematopoietic failure due to prolonged chemo-/radiotherapy or bone marrow infiltration by tumor cells, treatment with rhIL-3 leads to a clinically significant restoration of hematopoiesis, especially of thrombopoiesis and granulopoiesis. rhIL-3 has also been shown to improve neutrophil and platelet counts in patients with myelodysplastic syndromes, while improvement of hematopoiesis is rarely observed in patients with severe aplastic anemia with the presently used treatment schedules. Adverse effects of rhIL-3 are minor at the clinically used dosages and include fever, bone pain, headache, and stiffness of the neck. Transient thrombocytopenia has been observed in a few patients with myelodysplastic syndrome or aplastic anemia treated at dosages of 250-500 micrograms/m2. rhIL-3 is a multilineage hematopoietic cytokine with promising effects on platelet and neutrophil counts and special usefulness in patients with secondary hematopoietic failure.
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PMID:Clinical effects of recombinant human interleukin-3. 204 66

In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained.
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PMID:Effects of recombinant human interleukin-3 in aplastic anemia. 220 6

In a phase I/II study, 19 patients with advanced tumors but normal hematopoiesis and nine patients with bone marrow failure and prolonged severe cytopenias were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biological effects of this multipotential hematopoietic growth factor. Doses ranging from 30 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injection daily for 15 days. A dose-dependent increase in platelet counts ranging from 1.3-fold at 60 micrograms/m2 to 1.9-fold at 250 micrograms/m2 was induced by rhIL-3 in 15 of 18 evaluable patients with normal hematopoiesis. An increase in reticulocyte counts was observed in 14 patients. The blood leukocyte counts dose dependently increased 1.4- to 3.0-fold. In patients with bone marrow failure, platelet counts increased by a mean of sixfold (range, 1.3-fold to 14.3-fold) in five of eight evaluable patients. Reticulocyte counts increased 4.4-fold in six patients, and neutrophil counts increased by a mean of 3.1-fold in all eight patients. Platelet transfusions could be discontinued after treatment with rhIL-3 in two of three transfusion-dependent patients. Only mild side effects, mainly fever, headache, and flushing, were observed. These results indicate that rhIL-3 functions as a multilineage hematopoietin in vivo in patients with normal bone marrow function and in patients with secondary bone marrow failure.
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PMID:Effects of recombinant human interleukin-3 in patients with normal hematopoiesis and in patients with bone marrow failure. 238 50

Interleukin 3 (IL-3) is a hematopoietic growth factor with a pronounced thrombopoietic activity as well as a broad spectrum of activities on multipotent, committed and mature cells of different lineages. Available for clinical trials since 1989, IL-3 has been used in well over two thousand patients. In numerous phase I-II clinical trials, the tolerability profile and the various biologic activities have been defined, and ongoing phase III trials will finally establish its clinical relevance. Doses between 2.5 and 10 micrograms/kg/d given subcutaneously are well tolerated, cause low grade fever, occasional flu-like symptoms and headache. At these doses IL-3 enhances platelet and neutrophil recovery after cycles of myelotoxic chemotherapy, resulting in better adherence to the planned chemotherapy doses and schedules and a decrease in the need for platelet transfusions. Accelerated engraftment of platelets and neutrophils is seen with IL-3 also after bone marrow transplantation. The effect on neutrophil recovery can be enhanced by the use of a myeloid growth factor such as granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte (G)-CSF after five to 10 days of IL-3. Treatment enhancement is related to the effect of IL-3 on the proliferation of hematopoietic progenitors, which leads to an increase in target cells for GM- or G-CSF. Because of the increase in bone marrow proliferation, IL-3 is being used to increase the mobilization of progenitor cells to the blood and in bone marrow failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Present and future clinical relevance of interleukin 3. 769 63

The hematopoietic growth factor, recombinant human interleukin-3 (rhu IL-3), stimulates production of both leukocytes and platelets, and thus potentially has greater utility than growth factors that solely stimulate leukocytes production when employed with dose-intensive chemotherapeutic regimens. To determine the optimal schedule for administration of rhu IL-3 in combination with cyclophosphamide and carboplatin, an aggressive regimen for the treatment of advanced ovarian cancer, a phase I trial was initiated by the New York Gynecologic Oncology Group. Following surgical debulking, all patients received cyclophosphamide and carboplatin for 6 cycles. rhu IL-3 was administered at 50, 250, or 500 microgram subcutaneously for 5 days either immediately prior to or after administration of chemotherapy. Cohorts of six patients were treated at each dose level (three pre- and three postchemotherapy). Eighteen patients received 91 cycles of treatment. The major toxicities attributable to rhu IL-3 included fevers, chills, malaise, nausea, and headache, but were not dose-limiting at the doses of rhu IL-3 employed. The major finding of this study was that rhu IL-3 administered after chemotherapy offered greater platelet protection than rhu IL-3 administered prior to chemotherapy as assessed by median platelet nadir and duration of platelet counts < 50,000/mm3. A second major finding was a dose-response relationship for rhu IL-3: the two higher doses employed, 250 and 500 micrograms, offered more effective platelet protection than the lower dose employed, 50 micrograms. rhu IL-3 had no significant effects on leukocyte nadirs or duration of nadirs at any schedule or dose employed. rhu IL-3 may reduced the thrombocytopenia associated with aggressive treatment with cyclophosphamide and carboplatin, although this remains to be confirmed in a randomized, placebo-controlled trial. The effects of rhu IL-3 are dose- and schedule-dependent.
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PMID:A phase I trial of cyclosphosphamide and carboplatinum combined with interleukin-3 in women with advanced-stage ovarian cancer. 770 73

Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.
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PMID:Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression. 798 6


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