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

Ninety-nine patients with advanced epidemic Kaposi's sarcoma were treated with bleomycin-containing regimens: 30 received bleomycin and vincristine (BV) and 69 received doxorubicin, bleomycin, and vincristine. Treatment regimens were well tolerated, with response rates ranging from 76% to 81%. However, neutropenia developed even with the relatively nonmyelotoxic BV regimen. Twenty-eight of the 99 patients (28%) were evaluated for pulmonary function prior to, during, and after completion of combination chemotherapy to assess pulmonary toxicity commonly associated with bleomycin. The carbon monoxide diffusion capacity (DLCO) was the only measurement that showed significant changes prior to and after completion of therapy (P = .0003). Moreover, patients receiving more than 100 cumulative units of bleomycin experienced significantly greater declines in DLCO measurements than those receiving lower cumulative doses (P = .0067). No patient, however, developed clinically significant pulmonary toxicity attributable to bleomycin, with individual cumulative bleomycin doses ranging from 10 to 313 U (median, 112 U). We conclude that bleomycin is active and safe in the treatment of Kaposi's sarcoma, and close monitoring of pulmonary function is warranted with cumulative doses exceeding 100 U.
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PMID:Treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma using bleomycin-containing combination chemotherapy regimens. 138 42

To determine the safety, maximum tolerated dose, and preliminary efficacy of concomitant interferon-alpha and zidovudine therapy in AIDS-related Kaposi's sarcoma (KS), 56 patients with biopsy-proven KS and documented human immunodeficiency virus type 1 (HIV) infection were enrolled into a phase I study. Interferon-alpha was given intramuscularly at a dose of 9, 18, or 27 mu once a day and zidovudine was administered as 100 or 200 mg every 4 h for 8 weeks followed by a 48-week maintenance period. The major toxicities were anemia, neutropenia, and hepatotoxicity. Neutropenia was dose limiting with 1,200 mg of zidovudine/day and the lowest dose of interferon-alpha (9 mu/day). Hepatotoxicity was dose limiting with 27 mu of interferon and 600 mg of zidovudine/day. Cumulative dose-related anemia or neutropenia was not seen during long-term follow-up. The maximum tolerated doses for the combination were defined as 18 mu daily for interferon-alpha and 600 mg daily for zidovudine. Variable changes in CD4 lymphocytes occurred during the first 8 weeks of therapy. At higher doses of the combination, sustained increases in median CD4 lymphocyte numbers were noted (p less than 0.001). In HIV antigenemic patients, progressive antigen suppression was seen with increasing doses of the combination (p less than 0.005). The overall antitumor response rate was 47%. Tumor regression was associated with better survival benefits (p less than 0.001) and a pretreatment CD4 cell count greater than or equal to 200 cells/mm3 (p = 0.01). In conclusion, intermediate doses of interferon-alpha and lower doses of zidovudine appear to be relatively well tolerated and associated with disease improvement, including survival benefits.
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PMID:A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma. 167 May 85

Pilot studies were conducted to evaluate the toxicity and efficacy of two relatively marrow-sparing chemotherapy regimens in the treatment of advanced or progressive epidemic Kaposi's sarcoma. Chemotherapy regimens consisted of bleomycin (10 mg/m2), vincristine (1.4 mg/m2, 2 mg maximum) and Adriamycin (doxorubicin) at either 10 mg/m2 (Group I) or 20 mg/m2 (Group II). The therapy was given intravenously, every 2 weeks, until intolerable toxicity or maximum antitumor response. Thirty-three patients were treated. Although the patient populations were similar regarding pretreatment prognostic factors, the patients were not assigned randomly to these two treatment regimens. Major responses (complete or partial remission) were attained in 79% of the cases. The treatment-related toxicities consisted of mild to moderate nausea, hair loss, and peripheral sensory neuropathy. Bone marrow suppression consisted primarily of neutropenia (less than 1000/mm3) which occurred in a third of the patients. Variables significantly associated with shorter survival included hemoglobin (less than 10 g/dl), low Karnofsky performance status (less than 70%), and weight loss. Opportunistic infections occurred in the majority of cases during administration of chemotherapy, and were most likely related to severe cell-mediated immune dysfunction and low CD4-positive lymphocyte counts.
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PMID:Advanced acquired immune deficiency syndrome-related Kaposi's sarcoma. Results of pilot studies using combination chemotherapy. 168 9

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. 190 99

Combined zidovudine (ZDV) and interferon-alpha (IFN) is an appealing therapy for AIDS-associated Kaposi's sarcoma because of the antiretroviral as well as antitumor potential of this combination. Overlapping myelotoxicity of these agents, however, frequently complicates their clinical use. This phase I/II study was undertaken to test the safety and efficacy of granulocyte-macrophage colony stimulating factor (GM-CSF) in those patients who became neutropenic while receiving ZDV (1,200 mg/day) and IFN (9 MU/day). Despite a "high-risk" population of patients, the tumor response rate among evaluable patients was 50% (33% overall). Sixty-four percent of patients required GM-CSF and all patients receiving GM-CSF had a prompt improvement in their absolute neutrophil count (ANC). The use of GM-CSF was associated with an improved end of study ANC (p less than 0.05), but was not associated with tumor response, CD4 count improvement, or improved change in hemoglobin concentration. GM-CSF/ZDV/IFN was not associated with increased toxicity over ZDV/IFN; however, two unusual events occurred in the GM-CSF/ZDV/IFN group: erythema multiforme and glucose intolerance. Dose-limiting thrombocytopenia and anemia were seen in two patients and anemia in one patient on GM-CSF/ZDV/IFN. No consistent alterations in serum HIV p24 antigenemia were noted in either group. The use of GM-CSF mitigated the neutropenia of combined ZDV and IFN. Further study evaluating the utility of this hematopoietic growth factor in combination therapies for AIDS patients is warranted.
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PMID:GM-CSF as an alternative to dose modification of the combination zidovudine and interferon-alpha in the treatment of AIDS-associated Kaposi's sarcoma. 204 63

Thirteen men with a median age of 37 (range 28 to 46) years who had extensive Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS) were treated with combination chemotherapy and alpha-interferon. Four patients had stage III disease and nine had stage IV disease (one with pulmonary and eight with gastrointestinal involvement). Treatment consisted of monthly courses of actinomycin D, 1 mg/m2, and vinblastine sulfate, 6 mg/m2, given intravenously on day 1, bleomycin, 10 mg/m2 given intravenously on days 1 and 8, and human lymphoblastoid (alpha-) interferon, 10 million U/m2 given subcutaneously three times a week for six doses starting on day 14. Forty-one treatment cycles (median 3, range 1 to 12) were administered. The median granulocyte and platelet counts on day 14 before the start of interferon therapy were 600 X 10(9)/L and 134 X 10(9)/L respectively; the counts did not fall further during interferon therapy. There was no difference in T-cell subsets, 2',5'-oligoadenylate synthetase level or results of blastogenesis studies after interferon therapy. Four patients required admission to hospital for neutropenia-associated fever. A complete response (of 24 weeks' duration) was seen in one patient and a partial response (of 14 to 44 weeks' duration) in four. One patient had a mixed response, with regression of skin involvement but progression of pulmonary disease. The median length of survival was 48 (range 4 to 143) weeks. Eleven patients died of progressive Kaposi's sarcoma, one of lymphoma and one of Pneumocystis carinii pneumonia. The results suggest that this form of therapy is not appropriate for patients with Kaposi's sarcoma associated with AIDS.
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PMID:Combination chemotherapy and alpha-interferon in the treatment of Kaposi's sarcoma associated with acquired immune deficiency syndrome. 245 77

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.
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PMID:Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. 365 Mar 39

The efficacy and toxicity of doxorubicin, bleomycin and vindesine in epidemic Kaposi's sarcoma, and the role of rh GM-CSF in chemotherapy-induced neutropenia were evaluated in this Phase II study. Patients with progressive Kaposi's sarcoma were eligible, and were staged according to ACTG criteria. Treatment consisted of 20 mg/m2 doxorubicin, and a fixed dose of 15 mg bleomycin and 4 mg vindesine every 2 weeks. All patients continued antiretroviral medication with severe myelosuppression, patients received subcutaneous 5 micrograms/kg rh GM-CSF (Leucomax) from days 2-12. Response and toxicity were measured according to ACTG and WHO criteria. 27 patients were evaluable, 25 patients classified as having a poor prognosis. The response rate was 70% (3 CR, 16 PR), the duration of response was 18 weeks (range 8-25) and the median survival 30 weeks (range 4-63+). The cause of death was mostly opportunistic infection. 4 patients died of pulmonary Kaposi's sarcoma. The toxicity of this regimen was mainly myelosuppression and 13 patients were treated with rh GM-CSF. Complete recovery of the white blood cells occurred in seven of the 27 courses of rh GM-CSF (26%). No bacterial infections were recorded, but 5 patients (19%) developed an opportunistic infection during treatment. Peripheral neuropathy occurred in 16% of patients. Combination chemotherapy is effective in poor prognosis Kaposi's sarcoma but has a shortlasting effect. The main toxicity of this treatment is severe myelosuppression which can be ameliorated by rh GM-CSF. It remains to be established whether rh GM-CSF is also able to reduce the incidence of opportunistic infections.
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PMID:Treatment of poor prognosis epidemic Kaposi's sarcoma with doxorubicin, bleomycin, vindesine and recombinant human granulocyte-monocyte colony stimulating factor (rh GM-CSF). 753 34

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.
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PMID:Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. 760 42

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.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21


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