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)

We investigated whether paclitaxel was active in AIDS-associated Kaposi's sarcoma. We gave 135 mg/m2 intravenously over 3 hours every 21 days. Follow-up is available on the first 20 patients, most of whom had advanced Kaposi's sarcoma and severe immunocompromise. Neutropenia was the most frequent dose-limiting toxic effect; novel toxic effects included late fevers, rash, and eosinophilia. Creatinine increased in 2 patients and 1 patient had cardiomyopathy. There were 13 partial responses (65%, 95% CI 41-85%). All 5 patients with pulmonary involvement responded. Paclitaxel appears to be active against Kaposi's sarcoma as a single agent. Further studies, including a randomised trial, are warranted.
 ...
PMID:Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. 760 42

We conducted a Phase I trial to evaluate the safety, maximally tolerated dose (MTD), antitumor activity, and pharmacology of once-weekly oral etoposide in patients with Kaposi's sarcoma (KS) and AIDS. From September 1990 to October 1991, 27 eligible patients with biopsy-confirmed KS were treated at six etoposide dose levels, ranging from 150 to 400 mg weekly. Patients were treated until their tumor progressed or until unacceptable toxicity developed. On the first day of therapy, etoposide plasma concentrations were measured by high-performance liquid chromatography. The MTD was defined as the etoposide dose that induced reversible grade 3 toxicity in three of six patients during the first 4 weeks. Although dose-limiting toxicity was uncommon during the first 4 weeks of treatment (three of 27 patients), and the MTD was not reached, with longer treatment > 50% of patients developed dose-limiting toxicities, most commonly neutropenia. Responses were observed at all dosage levels (except 350 mg weekly), with partial tumor regression documented in nine (36%) of 25 evaluable patients. There was marked variability in etoposide area under the plasma concentration versus time curve, elimination half-time (t1/2), and urinary excretion. These pharmacokinetic features were not, however, associated with the presence of gastrointestinal symptoms, the severity of side effects, or tumor response. We conclude that weekly oral etoposide can be safely administered to patients with AIDS and KS. The observed antitumor effects over a wide range of doses support further studies with very low and minimally toxic etoposide doses, alone or in combination with other agents.
 ...
PMID:Weekly oral etoposide in patients with Kaposi's sarcoma associated with human immunodeficiency virus infection: a phase I multicenter trial of the AIDS Clinical Trials Group. 774 90

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
 ...
PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

Drug-related neutropenia is a common observation in AIDS patients. Haematological growth factors are therefore increasingly used in combination with myelotoxic agents to reduce the risk of infection and to improve the haematological tolerance of these regimens. We report a case of an AIDS patient with Kaposi's sarcoma who received GM-CSF for severe neutropenia due to anti-tumour chemotherapy combining alpha-interferon 2b and zidovudine. During GM-CSF administration there was a marked increase in the size of the Kaposi's sarcoma lesions as confirmed by ultrasonographic examination. As GM-CSF in vitro has been shown to promote Kaposi's sarcoma-like cell cultures, we discuss the potential role of this growth factor in increasing Kaposi's sarcoma lesions in vivo.
 ...
PMID:Possible role of granulocyte-macrophage colony stimulating factor (GM-CSF) on the rapid progression of AIDS-related Kaposi's sarcoma lesions in vivo. 794 90

Etoposide has been used in the treatment of a wide variety of neoplasms, including small-cell lung cancer, Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include the pretreatment leukocyte count, the performance status, the extent of prior erythrocyte transfusions, and the serum albumin level. In the past 7 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region. In addition, secondary acute lymphocytic leukemias (involving 11q23) have also been associated with prior epipodophyllotoxin exposure.
 ...
PMID:Pharmacodynamics and long-term toxicity of etoposide. 807 30

Neither single-agent therapy nor any combination treatment has been satisfactory enough to be regarded as standard in systemic advanced Kaposi sarcoma. In an attempt to achieve high efficacy in combination with low toxicity, we used a new liposomal formulation of doxorubicin. Pharmacologic data had established a long plasma half-life, an increased accumulation in tumor tissue, and a decrease in uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open-label, dose-escalating trial 40 male AIDS patients with advanced Kaposi sarcoma were enrolled to receive intravenous "stealth" liposomal doxorubicin biweekly at doses of 10 mg/m2 (n = 10), 20 mg/m2 (n = 27), and 40 mg/m2 (n = 3). The median CD4 count at baseline was 25/microL. After six cycles (12 weeks), 39 patients were evaluable. Three patients (7.5%) showed a complete response, which was histologically confirmed. A partial response was documented in 33 patients (85%). Stable disease was observed in three patients (7.5%). During a median treatment duration of 25 weeks, four patients developed stomatitis (10%), and four patients (10%) experienced alopecia. The most frequent hematologic toxicity was neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 toxicity was seen in 30%. Toxicity was dose-dependent and more frequent in the 40 mg/m2 stratum. During a median observation period of 25 weeks, opportunistic infections occurred in 57.5% of the patient population. We conclude that liposomal doxorubicin at dose levels of 10 and 20 mg/m2 is safe and effective for treatment of advanced Kaposi sarcoma in AIDS. A controlled trial comparing liposomal doxorubicin to conventional combination therapy is underway.
 ...
PMID:Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma. 815 40

This report describes the clinical spectrum and outcome of the hemophagocytic syndrome (HS) in 5 HIV infected patients. All 5 patients presented with fever, hepatomegaly and/or splenomegaly, confusion or coma and respiratory symptoms. Severe anemia was associated with thrombocytopenia and with neutropenia in 4 cases. Diffuse intravascular coagulopathy was present in 2 cases. Liver function tests were abnormal in three patients. The diagnosis of HS was made 2 to 12 weeks after the onset of symptoms and required in most patients repeated examinations of the bone-marrow, showing infiltration by histiocytes with prominent phagocytosis of blood cells. In one case this infiltration was not seen in the bone-marrow but only in the liver and the spleen. Varicella, mycobacterium infection, oesophageal candidiasis, Kaposi sarcoma were observed in the evolution of 3 patients. Anaplastic large cell Ki-1 lymphoma was present in one case. Four patients died as a result of complications of HS. The one patient with lymphoma survived.
 ...
PMID:[Hemophagocytic syndrome in HIV infection]. 824 41

We report a non-randomized Phase II clinical trial to assess the efficacy and safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were entered in the trial. Changes in size, colour and associated oedema of selected 'target' lesions were measured. Clinical, biochemical and haematological toxicities were assessed. Ten subjects were evaluated. A partial response was achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's sarcoma occurred in the remaining six, maintained until the end of the trial period in four. The drug was generally well tolerated, with few mild symptoms of toxicity. The main problem encountered was haematological toxicity, with three subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)/l). There was no evidence of cardiotoxicity. In this small patient sample, liposomal daunorubicin was an effective and well tolerated agent in the treatment of Kaposi's sarcoma.
 ...
PMID:Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study. 830 57

Sixteen patients with advanced AIDS-related Kaposi's sarcoma received liposomal doxorubicin (Doxil, Liposome Technology, Menlo Park, California) at 20 mg/m2 every 2 or 3 weeks in an open label study, and were evaluated for efficacy and toxicity. Eleven patients achieved a partial remission and five had stable disease. The median time to achieve a maximum response was two cycles (range 1-3) and the median duration of response was 14 weeks (range 6-30). Myelosuppression was the commonest adverse event; one patient was withdrawn because of neutropenia. Other adverse events were uncommon and mild. Liposomal doxorubicin is an effective and safe single agent treatment for advanced AIDs-related Kaposi's sarcoma.
 ...
PMID:Liposomal doxorubicin for treatment of AIDS-related Kaposi's sarcoma. 830 58

The efficacy of liposomal doxorubicin for treating Kaposi's sarcoma (KS) in patients infected with human immunodeficiency virus (HIV) was studied. Eight men with HIV infection and KS were to be given liposomal doxorubicin 20 mg/sq m i.v. monthly for six months and 10 mg/sq m i.v. monthly thereafter, depending on the response. They were assessed for the onset, extent, and duration of clinical response; relapse; adverse effects; development of new opportunistic infections; quality of life; and survival. Five patients had a clinical complete response (i.e., complete resolution of the manifestations of KS, as determined by physical examination but not confirmed by biopsy) and three patients had a partial response to the induction regimen of liposomal doxorubicin. Relapse occurred in all patients in whom therapy was stopped; reinstatement of therapy elicited a partial response. Neutropenia occurred in two patients; filgrastim therapy enabled the liposomal doxorubicin therapy to continue uninterrupted. Thromboembolic events developed or were suspected in three patients, although they may not have been caused by liposomal doxorubicin. Monthly i.v. administration of liposomal doxorubicin partially or completely eliminated the clinical manifestations of Kaposi's sarcoma in eight men infected with HIV.
 ...
PMID:Treatment of Kaposi's sarcoma with liposomal doxorubicin. 852 67


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