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 class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
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PMID:Clinical experience with CD64-directed immunotherapy. An overview. 943 76

We attempted to induce therapeutic immunity against prostate-derived tissues in patients suffering from progressive hormone-refractory metastatic prostate carcinoma. Thirteen patients were treated with two infusions, 1 month apart, of autologous dendritic cells (APC8015) preexposed ex vivo to PA2024, a fusion protein consisting of human granulocyte/macrophage-colony stimulating factor (GM-CSF) and human prostatic acid phosphatase (PAP). The infusions were followed by three s.c. monthly doses of PA2024 without cells. Three groups of patients each received PA2024 at 0.3, 0.6, or 1.0 mg/injection. All Ps were two-sided. Treatment was well tolerated. After infusions of APC8015, patients experienced only mild (grade 1-2) short-lived fever and/or chills, myalgia, pain, and fatigue. One patient developed grade 3 fatigue. Four patients developed mild local reactions to s.c. PA2024. Twelve patients were evaluable for response to treatment. Circulating prostate-specific antigen levels dropped in three patients. T cells, drawn from patients after infusions of APC8015, but not before, could be stimulated in vitro by GM-CSF (P = 0.0004) and PAP (P = 0.0001), demonstrating broken immune tolerance against these two normal proteins. Injections of PA2024 did not influence the reactivity of T cells against PAP and GM-CSF. However, antibodies to GM-CSF and, to a much lesser extent, to PAP reached maximum titers only after two or even three injections of PA2024, showing that directly injected PA2024 was involved in stimulation of humoral immunity. Dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity in prostate cancer patients, warranting further studies of this mode of immunotherapy.
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PMID:Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. 1087 66

The goal of this study was to evaluate, in patients with prostate cancer, the toxicity profile and biologic activity of the bispecific antibody MDXH210, which has specificity for the non-ligand-binding site of the high-affinity immunoglobulin G receptor (Fc gamma RI) and the extracellular domain of the HER-2/neu proto-oncogene product. Patients with prostate cancer that expressed HER-2/neu were entered into a phase I dose-escalation trial of MDXH210. Patients received an intravenous infusion MDXH210 during a period of 2 h three times per week for 2 weeks and were monitored for toxicity. Pharmacokinetic and pharmacodynamic parameters were measured and included the biologic end points of monocyte-bound MDXH210, cytokine production, and clinical response. Seven patients were treated with MDXH210 doses ranging from 1 to 8 mg/m2. In general, MDXH210 was well tolerated, with only mild infusion-related malaise, fever, chills, and myalgias. No dose-limiting toxic effects were observed. Biologic effects included induction of low plasma concentrations of tumor necrosis factor-alpha and interleukin-6 observed immediately after MDXH210 infusion and 70% saturation of circulating monocyte-associated Fc gamma RI with MDXH210 at a dose level of 4 to 8 mg/m2. Five of six patients had stable prostate-specific antigen levels during the course of 40 days or more. Circulating plasma HER-2/neu levels decreased by 80% at days 12 and 29 (p = 0.03 and 0.06, respectively, by the Wilcoxon signed rank test). MDXH210 can be given safely to patients with HER-2/neu-positive prostate cancer in doses of at least 8 mg/m2. At the doses studied, biologic activity was demonstrated and characterized by binding of MDXH210 to circulating monocytes, release of monocyte-derived cytokines, a decrease in circulating HER-2/neu, and short-term stabilization of prostate-specific antigen levels.
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PMID:Phase I pilot trial of the bispecific antibody MDXH210 (anti-Fc gamma RI X anti-HER-2/neu) in patients whose prostate cancer overexpresses HER-2/neu. 1121 Nov 51

Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist for the treatment of patients with prostate cancer in whom hormonal therapy is indicated. Two phase II trials and one phase III have been published as full papers in the literature. In the dose-finding phase II studies an initial dose of 240 mg degarelix sc followed by a monthly injection of 80 mg or 160 mg degarelix sc was sufficient to keep testosterone levels < or = 0.5 ng/ml. In a phase III trial it was demonstrated that degarelix was not inferior (in terms of testosterone suppression and prostate-specific antigen [PSA] decline) compared to standard hormonal therapy, ie, a GnRH agonist such as leuprolide. In fact, degarelix was associated with a faster testosterone suppression and PSA decline than leuprolide. Adverse events such as injection site reactions (40% vs <1%) and chills (4% vs 0%) were more commonly associated with degarelix. Also, degarelix is currently only available as one-month depot whereas in daily practice three-month depots (of GnRH agonists) are the preferred regimen. However, degarelix was recently approved by the US Food and Drug Administration for the treatment of advanced prostate cancer.
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PMID:Degarelix and its therapeutic potential in the treatment of prostate cancer. 1950 84

Hematospermia can be a distressing symptom for patients, but most cases are effectively managed by a primary care physician. Although the condition is usually benign, significant underlying pathology must be excluded by history, physical examination, laboratory evaluation, and, in select cases, other diagnostic modalities. In men younger than 40 years without risk factors (e.g., history of cancer, known urogenital malformation, bleeding disorders) and in men with no associated symptoms, hematospermia is often self-limited and requires no further evaluation or treatment other than patient reassurance. Many cases are attributable to sexually transmitted infections or other urogenital infections in men younger than 40 years who present with hematospermia associated with lower urinary tract symptoms. Workup in these patients can be limited to urinalysis and testing for sexually transmitted infections, with treatment as indicated. In men 40 years and older, iatrogenic hematospermia from urogenital instrumentation or prostate biopsy is the most common cause of blood in the semen. However, recurrent or persistent hematospermia or associated symptoms (e.g., fever, chills, weight loss, bone pain) should prompt further investigation, starting with a prostate examination and prostate-specific antigen testing to evaluate for prostate cancer. Other etiologies to consider in those 40 years and older include genitourinary infections, inflammations, vascular malformations, stones, tumors, and systemic disorders that increase bleeding risk.
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PMID:Evaluation and treatment of hematospermia. 2001 35