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)

To assess the clinical and hematopoietic effects of rhGM-CSF, a placebo-controlled double blind multicenter phase III study was undertaken in patients with non-Hodgkin's lymphoma receiving cytotoxic chemotherapy. Sixty-two patients who had granulocytopenia (< 1 x 10(3)/microliters) after the first cycle of chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone were enrolled. After the second cycle of chemotherapy with the same regimen, patients randomly received either rhGM-CSF (125 micrograms/m2/day) or placebo for 14 days (rhGM-CSF; 31 patients and placebo; 31 patients). Administration of rhGM-CSF induced a significant increase in granulocytes mainly with neutrophils, eosinophils and monocytes, but elevation of lymphocytes, platelets, and reticulocytes was not induced. Median days of granulocytes less than 1 x 10(3)/microliters in patients receiving rhGM-CSF were significantly shorter than in patients receiving placebo (p = 0.001). Adverse reactions encountered with rhGM-CSF, and observed in 58% of the patients were never life-threatening and always rapidly reversible. They included fever, nausea and vomiting, diarrhea, skin eruption, and malaise. These results suggest that rhGM-CSF can be safely administered to prevent neutropenia after chemotherapy in patients with non-Hodgkin's lymphoma.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) after chemotherapy in patients with non-Hodgkin's lymphoma; a placebo-controlled double blind phase III trial. 826 Aug 97

We studied the cardiopulmonary, hematologic, and inflammatory response to hemodialysis with seven different membranes in sheep. We also compared acetate dialysate with bicarbonate dialysate and evaluated the role of thromboxane in mediating these responses to dialysis with Cuprophan membranes (Baxter Healthcare Corp., Renal Division, Deerfield, Ill.) in sheep. The data generated in these studies indicate that dialyzer membranes can be divided into three major categories, defined by propensity to activate complement. High complement activators such as Cuprophan (low surface-area CF-1511 and high surface-area ST-25 dialyzers) produced dramatic neutropenia and hypoxemia and significant (p < 0.01) increases in the plasma concentration of thromboxane and in mean pulmonary artery blood pressure. The magnitude of these effects appeared to be surface area related. The low-flux Fresenius F-6 polysulfone membrane (Fresenius USA Inc., Concord, Calif.) also resulted in the generation of significant levels of C3a. In contrast, low complement activators such as polyacrylonitrile (AN-69; Gambro Hospal, Inc., Lakewood, Colo.) and cellulose triacetate (CT-110G; Baxter) produced little or no neutropenia, small transient increases in thromboxane, and no rise in mean pulmonary artery pressure. Dialyzers with intermediate complement-activating potential such as cellulose acetate (CA-110; Baxter) and Hemophan (HT-100; Baxter) produced small to moderate degrees of neutropenia and small increases in thromboxane and mean pulmonary artery pressure. Treatment of sheep with sodium ibuprofen before dialysis with Cuprophan CF-1511 membranes prevented the initial increases in mean pulmonary arterial pressure and thromboxane generation and the decrease in arterial oxygen tension, but did not affect the degree of complement activation or neutropenia. In sheep undergoing Cuprophan dialysis, bicarbonate dialysate did not prevent the increase in circulating complement and the associated neutropenia otherwise seen during the early portions of dialysis with acetate dialysate. Bicarbonate dialysate did, however, reduce (not prevent) the initial increases in thromboxane and mean pulmonary arterial pressure, and the magnitude of the hypoxemia seen with the use of acetate dialysate. The results of these experiments therefore indicate that (1) reactions in sheep correlate well with data collected in human beings and the model can be an effective means for comparing novel dialysis membranes and pharmacologic interventions during dialysis and (2) although complement appears to be the transducer of the hematologic and immunologic response, thromboxane appears to be the final effector of the cardiovascular responses to hemodialysis with Cuprophan membranes.
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PMID:Biocompatibility of hemodialysis membranes: evaluation in an ovine model. 843 36

To assess safety, antitumor response, and immunological and virological activity of interferon-alpha 2a and zidovudine combination therapy in patients with AIDS-related Kaposi's sarcoma, we conducted an open-label, Phase II, multicenter study. Sixty-three patients with biopsy-proven Kaposi's sarcoma and no previous interferon-alpha therapy received zidovudine 600 mg/day and interferon-alpha 2a 18 x 10(6) U/day. The median duration of follow-up was 49 weeks. Of 62 evaluable patients, 25 (40%; 95% confidence interval, 0.28-0.52) showed a complete (26%) or partial (15%) antitumor response. Eight of 30 patients (27%) with < 100 CD4 cells/mm3 and 17 of 32 patients (53%) with > or = 100 CD4 cells/mm3 had a response. The median time to response was 36 weeks. Of the 25 patients with a response, four developed tumor progression. The median duration of response was 22.4 weeks. Eight patients (13%) developed another AIDS-defining event and 13 (21%) died. The major toxicities included anemia (16%), neutropenia (27%), elevated serum transaminases (16%), weight loss (16%), malaise (14%), fatigue (14%), fever (10%), and headache (6%). Therapy with intermediate-dose interferon-alpha 2a and zidovudine resulted in tumor regression in patients with AIDS-related Kaposi's sarcoma who had a wide range of CD4 cell counts; this therapy was relatively well tolerated.
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PMID:A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group. 860 Dec 24

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1

A multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation. Cisplatin (35 mg/M2/day for 3 days) and etoposide (200 mg/M2/day for 3 days) were administered every 28 days for a planned 6 cycles of therapy. Sixteen of 37 evaluable patients (43%) responded to therapy. Myelosuppression was the dominant toxicity, with 89% of the patients experiencing grade 4 neutropenia, and nearly half grade 3 or 4 thrombocytopenia. Median survival was 8.5 months, with 30% of the patients alive at 1 year and 10% alive at 2 years. Malaise, fatigue, and peripheral neuropathy were the other major toxicities. The combination of etoposide at the dose of 200 mg/M2/day for 3 days and cisplatin at 35 mg/M2/day for 3 days is a highly potent combination against metastatic non-small cell carcinoma.
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PMID:Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study. 871 68

A late phase II study of LY188011 (gemcitabine hydrochloride), a new nucleoside derivative, in patients with non-small-cell lung cancer (NSCLC) was conducted at 24 Japanese institutions shown in Table 1 with a total of 69 patients enrolled. Of these, 67 were eligible and 64 completed at least one course of LY188011 therapy. The response rates (partial response only) in these populations were 20.9% (14/ 67) and 21.9% (14/64), respectively. Serious adverse reactions were septic shock and interstitial pneumonia in one patient each. Grade 3 or 4 adverse reactions included neutropenia (22.7%), decreased hemoglobin (13.4%), leukopenia (10.4%), anorexia (10.4%), malaise (7.5%), and nausea/vomiting (6.0%). Based on these results, it may be concluded that LY188011 has a high efficacy and benefit for the treatment of NSCLC.
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PMID:[A late phase II study of LY188011 (Gemcitabine hydrochloride) in patients with non-small-cell lung cancer. Gemcitabine Cooperative Study Group B for Late Phase II]. 888 45

An early phase II cooperative study of Gemcitabine Hydrochloride (abbreviated to "gemcitabine" herewith) was conducted in patients with a variety of solid tumors (i.e., lung cancer, gastric cancer, pancreatic cancer, colon/rectum cancer, cervical cancer, ovarian cancer and breast cancer) at 56 institutions. The aim of the first step (Step I) was to investigate the feasibility of gemcitabine in a variety of different solid tumors, including lung cancer regarding efficacy and safety. The aim of the second step (Step II) was as a result of step I (Responses were observed) to continue to investigate the efficacy and safety of gemcitabine in chemonaive patients with non-small cell lung cancer. As a Step I study, gemcitabine was administered once weekly at a dose of 800 mg/m2 for a consecutive 3-week period followed by a week of rest, in multiple courses. Among the 29 eligible patients with lung cancer, partial response (PR) was achieved in 3 patients (25.0%, 95% confidence interval: 5.5-57.2%) out of 12 chemonaive patients. Adverse reactions (grade 3 or higher) seen in 29 patients with lung cancer were neutropenia (27.6%), leukopenia (13.8%), decreased hemoglobin (13.8%), thrombocytopenia (10.3%), malaise (6.9%), anorexia (3.4%), nausea/vomiting (3.4%), diarrhea (3.4%), dyspnea (3.4%) and interstitial pneumonia (3.4%). In other types of solid tumors, PR was achieved in 2 (8.7%) out of 23 eligible patients with cervical cancer and in 1 (5.3%) of 19 eligible patients with ovarian cancer, while the use of analgesics became unnecessary in 1 patient with pancreatic cancer. Incidence as well as severity of main adverse reactions in these patients were comparable to those seen in patients with lung cancer. A Step II study, in which gemcitabine was administered once weekly at a dose of 1,000 mg/m2 to chemonaive patients with non-small cell lung cancer, was conducted, referring to the results of Step I and clinical studies conducted overseas. The results of the Step II study demonstrated PR in 5 (14.3%, 95% confidence interval: 4.8 - 30.3%) out of 35 eligible patients with non-small cell lung cancer and that the main adverse reactions were comparable to those seen in the Step I study, posing no tolerability problems in particular.
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PMID:[An early phase II study of gemcitabine hydrochloride (LY 188011). Gemcitabine Cooperative Study Group for Early Phase II]. 893 92

A late phase II study of LY188011 (gemcitabine hydrochloride), a new synthetic anticancer agent, was conducted at 20 Japanese institutions to evaluate the efficacy and safety of the agent administered alone in patients previously untreated with chemotherapy for primary non-small-cell lung cancer (NSCLC). All of the total 73 patients enrolled were eligible and 69 completed at least one course of LY188011 therapy. All patients were evaluated for safety. The response rate was 26.0% (19/73) of eligible patients. The most common adverse reactions included decreased hemoglobin, leukopenia, neutropenia, anorexia, nausea/vomiting, and malaise. Most adverse reactions were of grade 1 or 2 and only a few grade 3 or 4 reactions were reported. However, since a death occurred due to interstitial pneumonia, careful observation for this event is needed. Based on these results, it may be concluded that LY188011, a new anticancer agent, has adequate efficacy for the treatment of NSCLC and causes few clinically relevant adverse reactions.
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PMID:[Late phase II study of LY188011 (gemcitabine hydrochloride) in patient with non-small-cell lung cancer. Gemcitabine Late Phase II Cooperative Study Group A)]. 893 93

Bropirimine (U-54461S), an oral interferon (IFN) inducer that has also a direct antiproliferative activity, is a novel antitumor agent. To investigate the safety and pharmacokinetics of bropirimine tablets and to measure IFN concentrations in patients with cancer, Phase I studies were conducted. In single dose study (0.25 to 3g) and multiple-dose study with one-day dosing (1 or 2g, every one or two hours, three times a day), bropirimine treatment was well tolerated by the patients with cancer. In multiple-dose study with consecutive days dosing (1 or 2g, every 2 hours, three times a day for 3 or 5 consecutive days), a regimen with a dose of 1g orally administered every two hours, three times a day for three consecutive days was considered to be tolerable to cancer patients. Adverse drug reactions frequently observed were generalized malaise, fever, nausea/vomiting, anorexia, headache/dull headache, and tachycardia. Abnormalities in laboratory tests frequently observed were leukemia, neutropenia, thrombocytopenia, and elevation in GOT/GPT. IFN was not induced in any patients in the single dose study. It was, however, induced in 3 of 16 cases (18.8%) in the one-day dosing study and in 6 of 7 cases (85.7%) in the consecutive days dosing study. As to clinical antitumor efficacy, a decrease in size of the tumor lesions and improvement in subjective/objective symptoms were noted in two cases in the one-day dosing study. With these findings, the regimen with the dose of 1g orally administered every two hours, three times a day for three consecutive days with a four-day drug-free interval per week was recommended for early phase II studies.
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PMID:[Bropirimine (U-54461S) phase I clinical studies]. 897 2

Low-dose, subcutaneous recombinant human granulocyte colony-stimulating factor (rHuG-CSF, Lenograstim) was administered to 40 cancer patients (17 men, 23 women) enrolled from two medical centers to verify its clinical effectiveness and safety. The patients' mean age was 50.3 +/- 14.9 years. In this study, there were 20 patients with non-Hodgkin's lymphoma, 10 with breast cancer and 10 with various other solid tumors. The patients first received a course of chemotherapy without rHuG-CSF (control cycle). All patients had at least one episode of neutropenia or leukopenia during the control cycle. rHuG-CSF (2 micrograms/kg/day) was given subcutaneously for 10 days during the study cycle starting on the fourth day of chemotherapy. The nadirs of absolute neutrophil counts (ANC) were 1.8 +/- 0.25 x 10(9)/L and 0.27 +/- 0.05 x 10(9)/L for the rHuG-CSF cycle and pre-rHuG-CSF control cycle, respectively. The number of days of ANC < 1 x 10(9)/L were 1.03 +/- 0.29 and 7.38 +/- 0.58 for rHuG-CSF and control cycles, respectively. The duration from nadir to recovery of ANC (> or = 2 x 10(9)/L) was 9.68 +/- 1.15 days in the rHuG-CSF cycle, vs 22.53 +/- 1.03 days in the control cycle (p < 0.0001). No patient withdrew from the study. Adverse events were mild, with 12.5% to 40% of patients developing myalgia, general malaise, back pain, anorexia or fever. These side-effects were tolerable in all cases. The biochemical abnormalities were subtle and negligible. rHuG-CSF 2 micrograms/kg/day given subcutaneously for 10 days beginning on the fourth day of chemotherapy is very effective (90%), safe and convenient.
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PMID:Clinical trial of low-dose rHuG-CSF in neutropenic cancer patients following anti-cancer chemotherapy. 899 Jul 72


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