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)

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, +/- Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis. All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m2 subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 x 10(9)/L and 0.97 x 10(9)/L in cycle 1 as compared to 5.95 x 10(9)/L and 2.92 x 10(9)/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.
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PMID:A phase II study of recombinant granulocyte macrophage colony stimulating factor in patients with non-Hodgkin's lymphoma. 795 Sep 23

We conducted a multi-institutional (33 institutes), late phase II study with a 21-consecutive-day oral administration of etoposide for malignant lymphoma. Patient entry criteria were either those refractory to standard therapies or those for whom no appropriate therapy was available. A once-daily dose of 50 mg/body was administered for 21 consecutive days. Of the evaluable 83 among 88 entry patients, the overall response rate was 53.0% (44/83), including 10 CR; 52.5% (42/80, 9 CR) with non-Hodgkin's lymphoma and 100% (2/2, 1 CR) with Hodgkin's disease. Regarding abnormal laboratory findings, myelosuppression was observed; the incidence rates of leukopenia (23.3% with Grade 3), neutropenia (32.6%), hemoglobin decrease (17.4%) and thrombocytopenia (4.7%) were 70.9%, 65.1%, 54.7% and 19.8%, respectively. Major adverse reactions and their incidence were: anorexia 43.0%, alopecia 37.2%, nausea/vomiting 32.6%, fatigue 18.6%, stomatitis 15.1%, fever 7.0% and diarrhea 5.8%. Therefore, a 21-consecutive-day oral administration of 50 mg/body/day or 75 mg/body/day appears to be effective for the treatment of malignant lymphoma.
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PMID:[Late phase II study with 21-consecutive-day oral administration of etoposide for malignant lymphoma]. 799 16

During the period 1 January 1988 to 31 July 1991, 74 patients were seen with intermediate- or high-grade non-Hodgkin's lymphoma who were aged 70 years or over. Of these 74 patients, 20 were treated with radiotherapy alone, and 46 were judged as suitable for treatment with the chemotherapy regime MCOP (mitoxantrone, cyclophosphamide, vincristine and prednisolone). Involved field radiotherapy (35-40 Gy in 20 fractions over 4 weeks) was given to 14 of the 21 patients with stage IA and IIA disease, and 6 of the 25 patients with stage III and IV disease after completion of chemotherapy. The complete response rate was 63% at the completion of all treatment (6 months), and 39% at 12 months. There were no treatment-related deaths, and the 3-year cause-specific survival was 26% (overall survival 21%). For patients aged 70-75 years, the 3-year cause-specific survival was 34% in comparison to 17% for those patients aged 76-93 years. The chemotherapy was well tolerated by those patients aged 70 years and over, 70% of the patients did not vomit and no patients had significant vincristine neuropathy. There were only four infections associated with neutropenia. All patients completing six cycles had moderate, patchy alopecia. This MCOP regime is suitable for patients aged 70 years and over with intermediate- and high-grade non-Hodgkin's lymphoma. The survival of patients is comparable to that obtained with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with less apparent toxicity.
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PMID:Non-Hodgkin's lymphoma in elderly patients: a phase II study of MCOP chemotherapy in patients aged 70 years or over with intermediate- or high-grade histology. 799 22

High-dose chemotherapy regimens can cure a number of otherwise incurable diseases, such as Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, acute leukemia (in remission), and breast cancer. Trials of high-dose chemotherapy have generally used autologous bone marrow transplant or peripheral blood stem cell support to ensure hematologic recovery after intensive chemotherapy and/or radiation. This report describes an approach in which high-dose carboplatin chemotherapy was followed initially by granulocyte-macrophage colony-stimulating factor (GM-CSF; Escherichia coli. Sandoz-Schering, East Hanover and Kenilworth, NJ) and in subsequent patients, by both GM-CSF and repeated cycles of peripheral blood progenitor cell (PBPC) collection and administration. The addition of PBPC to this regimen led to significant reductions in the duration of neutropenia and thrombocytopenia, the requirement for erythrocyte and platelet transfusions, the length of hospital stay, and the use of intravenous antibiotics in this group relative to those patients who received GM-CSF alone. In addition, laboratory studies are presented that show a direct correlation between the number of progenitor cells reinfused and the duration of neutropenia and thrombocytopenia. The report also reviews data indicating that circulating progenitor cells are depleted by this approach. This suggests that the number of progenitor cells available for mobilization is finite. Finally, the magnitude of these effects, and their implications for future trials with repetitive cycles of dose-intensive therapy, are discussed.
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PMID:High-dose carboplatin chemotherapy with GM-CSF and peripheral blood progenitor cell support: a model for delivering repeated cycles of dose-intensive therapy. 810 54

Three children who developed pulmonary aspergillosis while being treated for leukaemia or non-Hodgkin's lymphoma. Each child continued with intensive myelosuppressive chemotherapy regimens during the infection and each was successfully treated with antifungal prophylaxis based on itraconazole by mouth. Amphotericin B was also given during periods of severe neutropenia. No reactivation of the fungal infection was seen.
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PMID:Chemoprophylaxis for pulmonary aspergillosis during intensive chemotherapy. 812 37

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

Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile neutropenic cancer patients. We noted in a previous study that response to empiric therapy was related more to disease classification (solid tumors vs. leukemia) than to the regimen chosen. In the present study we based empiric monotherapy on the underlying disease in treating 240 episodes of fever and neutropenia in 145 children. Patients with leukemia or Stage III/IV non-Hodgkin's lymphoma (higher risk group) were treated with imipenem-cilastatin, whereas those with solid tumors or Stage I/II non-Hodgkin's lymphoma (lower risk group) received ceftriaxone. The regimens were modified in 15% of lower risk and 45% of higher risk episodes. Overall successful outcomes were obtained in 93.2% of the higher risk (n = 119) and 97.5% of the lower risk (n = 121) episodes. The two groups differed significantly in duration of neutropenia, frequency of positive blood cultures and superinfection and the need for modification of the monotherapy (P < 0.05). Empiric monotherapy based on primary disease appears to be safe and effective for febrile neutropenic children with cancer at our Brazilian institution. Further studies will be needed before these findings can be generalized to patient populations in other settings.
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PMID:Fever and neutropenia in children with cancer: a therapeutic approach related to the underlying disease. 771 4

Two fatal infections caused by Scedosporium inflatum in immunocompromised patients are described. One patient developed peritonitis with this fungus 3 mths post renal transplantation. After a stormy course in the intensive care unit he eventually died. The other patient was suffering from non-Hodgkin's lymphoma and showed persistent neutropenia. Progressive deterioration occurred, and disseminated fungal infection was found at post mortem. Both isolates were resistant to all commonly available antifungal agents.
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PMID:Two fatal infections in immunocompromised patients caused by Scedosporium inflatum. 836 1

The nuclear enzyme topoisomerase I (topo I) has been recently recognized as the target for the anticancer drug camptothecin (CPT) and its derivatives. Two of the agents that target this enzyme--topotecan (TPT) and CPT-11--appear to be active against a broad range of human tumors. In the following presentation, we review 1) the role of topo I in normal cells, 2) the chemistry and proposed mechanism of action of CPT and its analogues, 3) the results of preclinical and clinical testing of TPT and CPT-11, and 4) mechanisms of resistance to these agents. In normal cells, topo I is thought to be involved in gene transcription and DNA replication. During the course of its normal catalytic cycle, topo I transiently forms a covalent bond with DNA. CPT and its derivatives slow the religation step of the enzyme and stabilize the covalent adduct between topo I and DNA. In S-phase cells, advancing replication forks convert these topo I-DNA adducts into double-strand breaks that appear to be responsible for the cytotoxicity of these agents. Preclinical studies demonstrate antineoplastic activity for TPT and CPT-11 in a variety of tumor models. Phase I studies have identified neutropenia as the dose-limiting toxicity for both drugs. Gastrointestinal effects might also be dose-limiting for CPT-11 administered on some schedules. CPT-11 has shown antitumor activity in phase II trials for patients with carcinomas of lung, cervix, ovary, colon, and rectum and for patients with non-Hodgkin's lymphoma. Phase II studies of TPT are in progress. Resistance to the cytotoxic effects of these agents might result from decreased production of topo I or from production of a mutated form of topo I. In addition, decreased metabolic activation of CPT-11 (which is a pro-drug) and active efflux of TPT by P-glycoprotein-mediated transport might contribute to resistance. As agents with a novel mechanism of action, tolerable toxicity, and encouraging antitumor activity in early clinical trials, TPT and CPT-11 are undergoing further clinical development. If these agents can be successfully combined with other active chemotherapy agents, the topo I-directed agents offer the potential for significant advances in the treatment of patients with a variety of malignancies.
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PMID:The current status of camptothecin analogues as antitumor agents. 838 Nov 86

Irinotecan hydrochloride (CPT-11), topotecan, sobuzoxane, NC-190, and IST-622 are unique topoisomerase inhibitors and are investigational in Japan. CPT-11 is a water-soluble, semisynthetic derivative of camtothecin. CPT-11 shows its anticancer activity by inhibiting topoisomerase I activity, now a target of anticancer agents with major interest. Recent clinical trials reveal that CPT-11 is very effective in the treatment of cancer including lung cancer, cervical cancer, ovary cancer, stomach cancer, colon cancer, and non-Hodgkin's lymphoma. Major dose limiting toxicities are leukopenia and diarrhea, and are dose related. Topotecan is an another semisynthetic derivative of camtothecin and is also topoisomerase I inhibitor. Topotecan has undergone phase I clinical evaluations in USA, europe, and recently in Japan. DLF are leukopenia and neutropenia. Topotecan is more hydrophilic than its parent compound and shows lesser protein binding. Renal excretion appears to be the major route of elimination. Sobuzoxane (MST-16) is a unique derivative of dioxopiperazine, an inhibitor of topoisomerase II. In phase II studies, definite anticancer effects are observed in patients with non-Hodgkin's lymphoma and adult T-cell leukemia/lymphoma. Responses are seen even in pretreated cases. Leukopenia is also dose-limiting. Non-hematologic toxicities are mild and include alopecia and G.I. toxicities. NC-190 is a novel benzophenazine derivative with excellent antitumor activities against murine tumors. NC-190 also inhibits topoisomerase II. Now the drug is an early clinical phase II studies in Japan. Toxicities include bone marrow suppression, transient mild to moderate liver enzyme elevation, alopecia and mild G.I. toxicities. Tumor responses are occasionally encountered. IST-622 is a semisynthetic derivative of chartreusin. The drug is an inhibitor of topoisomerase II (and I in high concentration). IST-622 shows excellent, broad anticancer activity against murine tumors. The drug is well absorbed from small intestine. IST-622 is now in phase I clinical trial in Japan.
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PMID:[Topoisomerase inhibitors developing in Japan]. 842 86


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