Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anemia, thrombocytopenia, and neutropenia are common manifestations in patients with human immunodeficiency virus infection that become more frequent and severe with progression from the asymptomatic state to acquired immunodeficiency syndrome (AIDS). Causes of anemia in AIDS include nutritional deficiencies, infection, and marrow suppression by antiretroviral drugs and by the disease itself. Autoimmune hemolysis and blood loss from gastrointestinal lymphoma or Kaposi sarcoma may also contribute. Granulocytopenia may be due to infection, autoimmunity, or bone marrow suppression by drugs or the immunodeficiency virus. Lymphopenia, the classic hallmark of the disease, typically affects T-helper cells first and worsens as the disease advances. Lymphopenia is a result of the direct cytopathic effects of the virus. Thrombocytopenia can occur from antibodies causing an idiopathic thrombocytopenic purpura-like state from bone marrow suppression or from thrombotic thrombocytopenic purpura. A prolonged partial thromboplastin time due to a coagulopathy caused by lupus anticoagulant causing has been described. A variety of malignancies occurs.
 ...
PMID:Hematological Effects of Human Immunodeficiency Virus Infection. 1088 19

Chronic oral VP-16 (etoposide) is a chemotherapy regimen with a wide application in oncology and documented efficacy against germ cell tumors, lymphomas, Kaposi's sarcoma, and primary brain tumors. This study was performed to assess the toxicity and activity of chronic oral etoposide in the management of children with recurrent intracranial nondisseminated ependymoma. Twelve children (median age of 8 years) with recurrent ependymoma who were refractory to surgery, radiotherapy, and chemotherapy (carboplatinum or the combination of procarbazine, lomustine, and vincristine) were treated with chronic oral etoposide (50 mg/m(2)/day). Treatment-related complications included the following: alopecia (10 children), diarrhea (6), weight loss (5), anemia (4), neutropenia (3), and thrombocytopenia (3). Three children required transfusion (two with packed red blood cells; two with platelets), and two children developed neutropenic fever. No treatment-related deaths occurred. Six children (50%) demonstrated either a radiographic response (two children, both with partial response) or stable disease (four children) with a median duration of response or stable disease of 7 months. In this small cohort of children with recurrent intracranial ependymoma, oral etoposide was well tolerated, produced modest toxicity, and had apparent activity.
 ...
PMID:Recurrent intracranial ependymoma in children: salvage therapy with oral etoposide. 1127 60

The aim of this study was to examine the outcome, adverse events and clinical complications of long-term chemotherapy with pegylated liposomal doxorubicin (PegLiposomal DOX) for human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) in the pre-highly active antiretroviral therapy (HAART) era. A phase II study over a 4-year period in a tertiary care university hospital was carried out. 52 acquired immunodeficiency syndrome (AIDS)-patients with advanced KS received long-term chemotherapy (71+/-51 weeks) with a mean of 22.8+/-18.2 cycles and a mean cumulative liposomal doxorubicin dose of 456+/-364 mg/m(2) (120-1040 mg/m(2)). Tumour burden, duration and dosage of PegLiposomal DOX, adverse events, opportunistic infections, immunological parameters and HIV load were measured. A complete (10%) or partial response (56%) was achieved while on chemotherapy. 10 patients (19%) showed stable disease. Tumour progression was observed in 8 patients (15%). Importantly, chemotherapy with PegLiposomal DOX was also successful after previous cytostatic therapy with bleomycin and vincristine. The most common adverse events included leucopenia, neutropenia, anaemia, and increased liver function tests. 34 patients (65%) developed new opportunistic infections and 29 patients (56%) died during the study period. To conclude, pegylated liposomal doxorubicin is a safe and effective drug for long-term chemotherapy of advanced (AIDS) KS without adverse effects on CD4 cell counts and HIV viral load.
 ...
PMID:Long-term chemotherapy of HIV-associated Kaposi's sarcoma with liposomal doxorubicin. 1131 76

The Food and Drug Administration (FDA) has recently granted accelerated approval to Liposome Technology, Inc., to market DOX-SL for people with AIDS with refractory Kaposi's sarcoma (KS). DOX-SL, an intravenous drug, is a new form of a regular cancer chemotherapy called doxorubicin, and has dosing schedules similar to standard chemotherapy. The drug, encapsulated in lipid membranes (liposomes), will enable doxorubicin to be delivered directly in a higher concentration to KS lesions, with fewer systemic side effects. The drug will likely be used in combination with standard chemotherapy. Side effects include: hair loss, nausea, and neutropenia. This is the first time the FDA has ever approved a drug for KS.
 ...
PMID:KS update. 1136 82

Vestar has asked for a second time for Food and Drug Administration (FDA) approval of DaunoXome, a liposomal daunorubicin, for the treatment of patients with systemic Kaposi's Sarcoma (KS) based on results from a large phase III trial. Overall response rates were lower than expected in this trial, with only 23 percent responding to DaunoXome, and there were slightly more than expected cases of reported neutropenia. However, incidence of toxicity such as hair loss, fatigue, and neuropathy were significantly lower. One other liposomal anthracycline, Doxil, has also been recommended for approval. No trials as yet have been done to compare the two drugs' effectiveness, although quality-of-life issues make these drugs attractive candidates.
 ...
PMID:Liposomal chemotherapies. 1136 53

DOXIL, a liposomal form of the chemotherapy drug doxorubicin which allows higher concentrations to be delivered to Kaposi's sarcoma (KS) lesions or cancer tumors, has been approved by the Food and Drug Administration (FDA). The guidelines for DOXIL are the same as doxorubicin. Both may be toxic to the heart and other toxicities can occur, including neutropenia. DOXIL is given by intravenous infusion and stays in the bloodstream much longer than doxorubicin. Sequus Pharmaceuticals, Inc., the developer of DOXIL, received faster FDA approval by requesting approval only for patients who are intolerant to other chemotherapy. The company will request first-line use approval now that more data is available. A potential competitor is NeXstar Pharmaceuticals' DaunoXome.
 ...
PMID:DOXIL approved for KS. 1136 51

We wished to evaluate the efficacy and safety of a low and an intermediate daily dose of interferon-alpha2b (IFN-alpha2b) with didanosine in patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). HIV-seropositive subjects with biopsy-confirmed cutaneous KS were randomized to receive either a low (1 million IU) or an intermediate (10 million IU) dose of IFN-alpha2b once daily with twice daily doses of didanosine. Treatment assignment was stratified by CD4 count. Response, toxicity, changes in CD4 counts, and survival were evaluated. Sixty-eight eligible subjects were accrued, 35 to low-dose and 33 to intermediate-dose IFN-alpha2b. The response rate was 40% in the low-dose group (95% CI, 24-58) and 55% in the intermediate-dose group (95% CI, 36-72) (p = 0.338). The median response duration was approximately 110 weeks in both groups. Intermediate-dose IFN induced grade 3/4 neutropenia more often (21% vs. 3%, p = 0.048) and grade 3/4 toxicity faster (p = 0.0231) and necessitated treatment discontinuation earlier for drug-related toxicities (p = 0.0416) than low-dose IFN. There were no significant differences in survival between the treatment groups. Baseline CD4 count was the only significant factor predicting response. Once-daily low-dose and intermediate-dose IFN-alpha2b induced similar response rates, which were achieved without optimal antiretroviral therapy. The slightly higher response rate in the intermediate-dose group was offset by its significantly poorer tolerance. These findings justify the use of lower, well-tolerated IFN doses for treatment of KS with currently used antiretroviral regimens.
 ...
PMID:Efficacy of low-dose interferon with antiretroviral therapy in Kaposi's sarcoma: a randomized phase II AIDS clinical trials group study. 1203 36

Kaposi's sarcoma (KS), the most common malignancy associated with HIV infection, is caused by the Kaposi sarcoma herpesvirus (KSHV). Exacerbations of KSHV are associated with increased human interleukin-6 (HuIL-6), and elevated IL-6 could be related to the development of KS. IL-4, a cytokine with pleiotropic effects, suppresses IL-6 in vivo and modestly inhibits AIDS-KS-derived cells in vitro. Suppression of IL-6 by exogenous IL-4 could result in antitumor activity. We report the results of a clinical trial to test this hypothesis. A phase I/II dose escalation safety, tolerance, and efficacy trial was conducted in patients with biopsy-proven AIDS-related KS, at two university medical centers. Patients were scheduled to receive IL-4 (0.5, 1.5, 3.0, or 4.0 microg/kg/day) administered subcutaneously (s.c.) in sequential cohorts. Patients were continued on study as long as the drug was tolerated or the disease progressed. Patients were followed for antitumor activity, effects on viral replication, immune status, and clinical and laboratory toxicity. Seventeen patients were enrolled at two sites over a 21-month period. There were 15 males and 2 females, and 1 patient was Hispanic. All patients had a Karnofsky score >70. Patients enrolled only into the two lower dose cohorts (0.5 and 1.5 microg/kg/day). Both groups had similar baseline characteristics. The median time on treatment was only 7.4 and 8.4 weeks for the 0.5 and 1.5 microg/kg/day dose levels, respectively. There was significant neutropenia, with 6 patients having grade 3 or greater toxicity requiring granulocyte colony-stimulating factor (G-CSF). Three patients on a dose of 1.5 microg/kg/day stopped treatment due to protocol-defined toxicity. There were no appreciable effects on CD4/CD8 counts. HIV viral RNA did not significantly change over time. However, in several people, it appeared to decline with treatment and rebound with discontinuation of treatment. Corresponding changes were noted in the HIV immunocomplex dissociated (ICD) p24 antigen. One patient had a partial response, 11 patients had stable disease, and 5 patients had disease progression during the short period of treatment. The maximum tolerated dose for IL-4 in patients with advanced AIDS-related KS is 1.5 microg/kg/day. At this dose level, IL-4 is poorly tolerated and is not an effective KS treatment. Treatment of the majority of patients is discontinued because of drug-related toxicity or because of disease progression. Future studies of IL-4 should be confined to studies of cytokine manipulation of the underlying HIV infection, as there appears to be little antitumor activity.
 ...
PMID:Lack of antitumor activity and intolerance of interleukin-4 in patients with advanced HIV disease and Kaposi's sarcoma. 1251 14

We evaluated the safety and maximum tolerated dose of interferon (IFN)-alpha2b in combination with protease inhibitor-based highly active antiretroviral therapy (HAART) in a phase 1 study in 14 patients with AIDS-associated Kaposi sarcoma (KS). Planned IFN dose levels were 0, 1, 5, 10, and 15 million IU administered by daily subcutaneous injection. Dose-limiting toxicities were neutropenia and malaise. The maximum tolerated IFN dose was 5 million IU/d. The median CD4 count increased from 260 cells/muL at baseline to a maximum on-study value of 359 cells/muL. In 6 patients with paired baseline and on-study values, the median HIV RNA level decreased from 20,179 copies/mL to a minimum on-study value of 309 copies/mL. Of 13 patients whose KS response could be evaluated, 5 showed objective tumor regression. Responses occurred in HAART-experienced and HAART-naive subjects. Five patients, including 2 responders, 2 with stable KS, and 1 with progression, had serial measurements of Kaposi sarcoma herpesvirus (KSHV) load. None of these patients, irrespective of treatment arm or KS response, showed durable clearance of KSHV from plasma or peripheral blood mononuclear cells. This study establishes a safe dose of IFN that can be used with HAART and, potentially, with other inhibitors of KS in future clinical trials.
 ...
PMID:Interferon-alpha2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma: an AIDS malignancy consortium phase I trial. 1639 45

Interleukin-12 (IL-12) enhances Th1-type T-cell responses and exerts antiangiogenic effects. We initiated a phase 1 pilot study of IL-12 in 32 patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) whose KS was progressing while on antiretroviral therapy. Fifteen patients had poor prognosis T(1)S(1) disease. IL-12 was administered subcutaneously twice weekly at doses from 100 to 625 ng/kg. The maximum tolerated dose was 500 ng/kg, and the principal toxicities were flulike symptoms, transaminase or bilirubin elevations, neutropenia, hemolytic anemia, and depression. No tumor responses were seen at the lowest dose (100 ng/kg), but 17 of 24 evaluable patients at the higher doses had partial or complete responses (response rate, 71%; 95% confidence interval, 48%-89%). Only 3 of 17 patients had a change in antiretroviral therapy before responding, and there were no significant differences between responders and nonresponders with regard to changes in CD4 counts or viral loads. Patients had increases in their serum IL-12, interferon-gamma, and inducible protein-10 (IP-10) after the first dose, and increases above baseline persisted after week 4. These results provide preliminary evidence that IL-12 has substantial activity against AIDS-related KS with acceptable toxicity and warrants further investigation for this indication.
 ...
PMID:Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. 1650 79


<< Previous 1 2 3 4 5 6 Next >>