Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085593 (chills)
 4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Interleukin-1 alpha (IL-1 alpha) can act as both a hematopoietic growth factor and a stimulant of cellular and humoral immune responses. To promote acceleration of hematologic recovery and induce immune antitumor activity, we initiated a phase I/II dose escalation trial of 6-hour daily infusions of recombinant human IL-1 alpha after autologous transplantation. Forty patients with Hodgkin's disease (n = 9) and non-Hodgkin's lymphoma (n = 31) transplanted with unmobilized autologous peripheral blood stem cells or bone marrow stem cells received daily 6-hour infusions of IL-1 alpha (day 0 to day +13) at daily doses between 0.1 to 10 micrograms/m2/d; 7 patients received only 7 planned days of IL-1 alpha (day 0 through 6). Most patients received all 14 days of therapy, although 5 patients discontinued treatment early (after 1 to 6 doses) because of fever and severe chills. Toxicity included IL-1 alpha-related fever (occurring on a median of 9 of 14 treatment days), fatigue, and severe chills. Hypotension was dose-limiting and led to discontinuation of IL-1 alpha in both patients receiving 10 micrograms/m2/d. IL-1 alpha-treated patients receiving 3.0 micrograms/m2/d (the maximum tolerated dose) achieved neutrophil recovery (absolute neutrophil count greater than 500/microL) significantly earlier (median, 12 days; range, 11 to 27) than untreated control patients or those receiving IL-1 alpha at 0.1 to 1.0 micrograms/m2/d (median, 27; range, 9 to 63; P < .0001). In addition, the IL-1 alpha patients' bone marrows at day +14 were significantly enriched with committed myeloid progenitor cells. Strong trends to earlier freedom from red blood cell (P = .06) and platelet (P = .09) transfusions were also noted after IL-1 alpha treatment. This earlier hematopoietic engraftment after 3.0 micrograms/m2/d IL-1 alpha allowed earlier hospital discharge (median, 25 v 37 days for control or low-dose IL-1 alpha patients [P < .0001]) and a concomitant reduction (by $38,000) in median hospital charges (P = .01). The clinical toxicities of IL-1 alpha infusion are substantial, though not life-threatening. The accelerated hematopoiesis and immune response activation observed in this trial suggest the value of its further investigation in controlled trials and perhaps in combination with other hemopoietins after transplantation.
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PMID:Interleukin-1 alpha administered after autologous transplantation: a phase I/II clinical trial. 791 16

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

Recombinant human interleukin 3 (rhIL-3, expressed in Escherichia coli) is a hematopoietic growth factor with protean biological effects on bone marrow in animal models, including enhanced granulocyte and platelet production and the capacity to ameliorate chemotherapy-induced bone marrow toxicity. We, therefore, undertook a Phase I trial in patients with advanced solid tumors and normal bone marrow function. Cohorts of four to six patients each received daily s.c. doses of rhIL-3 (SDZ-ILE-964; Sandoz) at dose levels of 1. 0, 2.5, 5.0, and 10.0 microgram/kg according to the following schedule: cycle 1, rhIL-3 days 1-14; cycle 2, carboplatin (350 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1-3; and cycle 3, carboplatin (350 mg/m2) on day 1, etoposide (100 mg/m2) on days 1-3, and rhIL-3 on days 4-17. Each cycle was a total of 28 days. An analysis of 20 patients entered into all four escalating dose levels revealed that, during cycle 1, absolute neutrophil count (ANC) increased from a median baseline of 6,643/mm3 to a median of 12,692/mm3, and platelets increased from a median baseline of 314,000/mm3 to a median of 465,000/mm3. When cycle 2 was compared with cycle 3, the median ANC nadir increased from 192/mm3 to 988/mm3, and the mean ANC nadir increased from 458/mm3 to 1,297/mm3. Median platelet count nadirs increased from 29,000/mm3 to 84,000/mm3, and the mean nadir platelet counts increased from 72,000/mm3 to 129,000/mm3. Total days on which platelets were <50,000/mm3 was 52 for cycle 2 and 19 for cycle 3. The maximum tolerated dose of rhIL-3 was 5.0 microgram/kg/day; dose-limiting toxicities included fatigue, chills, fever, and headache. These data suggest a clear but variable biological activity observed with IL-3, as measured by the reduction in the depth and duration of thrombocytopenia and/or neutropenia when cycle 2 was compared with cycle 3. rhIL-3 is a promising cytokine that may help to ameliorate the bone marrow toxicity observed with the use of chemotherapeutic agents.
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PMID:Phase I trial of recombinant interleukin 3 before and after carboplatin/etoposide chemotherapy in patients with solid tumors: a southwest oncology group study. 981 5