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)

According to cell cycle synchrony principles, bleomycin was infused for 48 hours, followed by a dose of either methotrexate or hydroxyurea after a 24-hour rest, in 36 adult patients with disseminated carcinoma. In this preliminary study, a 59% response rate was noted among patients with epidermoid carcinoma of the head and neck. Four of four patients with transitional cell carcinoma of bladder and one patient with hypernephroma also responded. No responses were noted among five patients with epidermoid carcinoma of the lung. The length of response ranged from 1 to 8 months (median, 2 months). Seventy-seven percent of the responders had extensive prior radiotherapy. The first patient treated had fatal sepsis with leukopenia, which prompted a widening of the treatment interval. Subsequently, toxicity was mainly mild or absent, the moderate or severe toxicity was primarily neutropenia, which was reversible. The use of low-dose bleomycin infusion is safe and may play a role in cancer therapy in combination with other agents specific for certain tumors. The length of infusion should be determined by the cell cycle of the tumor, if its potential synchronizing capabilities are to be exploited.
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PMID:Intravenous bleomycin infusion as a potential syncronizing agent in human disseminated malignancies: a preliminary report. 6 5

Multiple infections and severe neutropenia were found in a previously healthy 29 year old man with no history of similar syndromes in the family, drug ingestion or exposure to environmental toxins. There was no evidence at the time of presentation of diseases previously associated with agranulocytosis (e.g., neoplasia, thyrotoxicosis, chronic infection, collagen-vascular disease or leukoagglutinating antibody). His serum contained a nonagglutinating, complement-dependent, cytotoxic antibody, however, reactive with peripheral blood granulocytes from 35 per cent of normal donors. The neutropenia was not affected by steroids but resolved promptly after splenectomy. Microscopic examination of the spleen revealed ingestion of polymorphonuclear leukocytes by splenic macrophages. Family studies indicated that the target antigen was non-HLA and that the antibody was not absorbed by lymphocytes or platelets. We conclude that the agranulocytosis was autoimmune in origin and suggest that similar myeloid-specific immune responses could influence granulocyte tranfusion and bone marrow transplantation by alloimmune "rejection" that would not be avoided by matching only for HLA specificities.
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PMID:Acquired agranulocytosis with granulocyte specific cytotoxic autoantibody. 44 60

A phase II study of vindesine was carried out in 33 patients with colorectal cancer and nine patients with esophageal cancer. With the exception of six previously untreated patients with esophageal cancer, all others were refractory to 5-FU-containing regimens, w,hich included vincristine in ten patients. The initial dose of vindesine was 4 mg/m2 administered intravenously over 30 min every 2 weeks. Tumor regression less than 50% was set patients (six colorectal and two esophageal) achieved minor responses. Prior treatment with vincristine did not seem to influence response to vindesine. In general, the treatment with vindesine was well tolerated. The hematologic toxicity was acceptable and manifested mainly as moderate and transient neutropenia. The major nonhematologic toxicity was peripheral neuropathy, which became limiting. It occurred in 33% of patients who received two or more courses of vindesine. Because of the apparent antitumor activity and dose-limiting neurotoxicity of vindesine in this sutdy, further investigations of this compound should be conducted in combination chemotherapy programs for patients with metastatic gastrointestinal cancers.
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PMID:Phase II evaluation of vindesine in the treatment of colorectal and esophageal tumors. 45 86

Methyl-CCNU, a compound with marked antitumor activity against the solid Lewis lung tumor in mice, was submitted to a preclinical pharmacologic evaluation. The toxicity of a single iv infusion was tested in 37 beagle dogs and 21 rhesus monkeys. The minimum lethal dose (LD) in dogs was 14 mg/kg and five of six dogs died within 7-10 days after treatment from hematopoietic toxicity with neutropenia, lymphopenia, anemia, and concomitant sepsis. Metaplasia of the intestinal epithelium also occurred. Thrombocytopenia was not observed. Dogs treated with 9.27-1.56 mg/kg exhibited reversible neutropenia and lymphopenia but survived without severe morbidity or histopathologic lesions. In monkeys, interstitial nephritis was the treatment-limiting toxicity and three of six monkeys treated with 45 or 30 mg/kg died, became moribund, or exhibited severe renal histopathologic lesions. One monkey treated with 45 mg/kg had degeneration of the testes. Survivors exhibited reversible toxicity and no histopathologic lesions. Treatment with doses as low as 7.5 mg/kg caused reversible neutropenia, lymphopenia, and anemia. The largest nontoxic dose for a single iv infusion was 3.12 mg/kg (62.40 mg/m2) for the dog and 3.75 mg/kg (45 mg/m2) for the monkey. These and earlier observations showed that methyl-CCNU had approximately one third the toxicity of CCNU. Methyl-CCNU also did not cause the delayed hepatic toxicity which is characteristic of CCNU treatment in the dog.
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PMID:Methyl-CCNU: preclinical toxicologic evaluation of a single iv infusion in dogs and monkeys. 82 19

GM-CSF represents an important advance in bone marrow transplantation. The drug can be given safely and does not appear to increase the risk of graft-versus-host disease or tumor relapse. This is a rare example of a new technology reducing the cost of health care. By shortening the duration of hospitalization, GM-CSF can significantly reduce the cost of a bone marrow transplant (Table 2). However, there are few data to support the conclusion that the reduction in the duration of neutropenia is associated with a superior survival. This attests to the excellent supportive care that has been developed for patients undergoing bone marrow transplantation. At present, GM-CSF has become a standard therapy in autologous bone marrow transplantation. However, the future will undoubtedly see the development of combinations of hematopoietic growth factors and/or new growth factors that will further improve our ability to perform bone marrow transplantation.
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PMID:The use of granulocyte-macrophage colony-stimulating factor in bone marrow transplantation. 136 21

To evaluate the clinical effect by administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy in non-Hodgkin malignant lymphoma (NHL), 17 patients with NHL were subjected to this study. Administration of rhG-CSF ameliorated the decrease in absolute neutrophil counts after the cytotoxic chemotherapies and activated neutrophil functions in active oxygen product and expressions of adhesion proteins. To consistent with these results, rhG-CSF administrations post cytotoxic chemotherapy were effective for reducing infection complications associated with neutropenia. Furthermore, administration of rhG-CSF increased peripheral hematopoietic progenitor cells, thus suggesting promising therapeutic potential for autografting. Recently, it has been reported that blood neutrophils may synthesize mRNA and proteins important in inflammation including various cytokines such as IL-1, IL-6, TNF-alpha and IFN-alpha, but, administration of rhG-CSF showed no obvious effect on the level of either IL-1, IL-6, TNF-alpha or IFN-alpha in sera, and furthermore, the in vitro stimulation by rhG-CSF induced no significant production of these cytokines and expressions of TNF-alpha and IFN-alpha mRNAs. Finally, we studied on anti-tumor effect of administration of rhG-CSF in CDF1 mice inoculated with syngeneic lymphoma cells. rhG-CSF infusion suppressed the liver metastasis and prolonged the overall survival, thus suggesting the hypothesis that use of rhG-CSF in some patients with NHL might control the disease through stimulating both production and functional activation of neutrophils.
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PMID:[In vivo effects on human neutrophils by administration of rhG-CSF and clinical significance]. 137 67

The differential diagnosis of unexpected neutropenia following bone marrow transplantation includes several potentially life-threatening complications including graft rejection, overwhelming infection, relapse of the underlying neoplasm, and intrinsic graft failure. However, a number of recent reports document that the differential diagnosis also includes autoimmune neutropenia, which, although potentially life-threatening, often responds well to corticosteroids or splenectomy. Autoimmune neutropenia has been reported following both autologous and allogeneic bone marrow transplantation. Herein we report a 31-year-old woman who developed a rapidly falling neutrophil count 11 days following peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. A laboratory evaluation supported a diagnosis of autoimmune neutropenia, and the neutropenia resolved following treatment with steroids and granulocyte-colony stimulating factor.
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PMID:Autoimmune neutropenia following peripheral blood stem cell transplantation. 138 19

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.
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PMID:Phase II trial of suramin in patients with advanced renal cell carcinoma: treatment results, pharmacokinetics, and tumor growth factor expression. 139 2

CI-973, a platinum(II) derivative with a 2-methyl-1,4-butanediamine carrier ligand, has activity in cisplatin-resistant tumor models in vitro and in vivo. In a Phase I pharmacokinetic study, 31 patients were treated with CI-973 (24 to 50 mg/m2/day for 5 days; 28-day cycles) given i.v. over 30 min without routine antiemetic prophylaxis or hydration. Of the 29 patients evaluable for maximum tolerated dose determination, most had a performance status of 0 or 1, and most had received prior chemotherapy. Neutropenia was dose limiting at 40 and 50 mg/m2/day. Recovery from neutropenia was generally rapid with nadir counts and recovery usually occurring by Days 15 and 22, respectively. Drug-associated thrombocytopenia was uncommon and never severe, even in patients with Grade 4 neutropenia. Anemia was common, but did not appear dose related. Drug-related nausea and vomiting and changes in renal function were relatively infrequent and mild. No clinically evident ototoxicity was reported, although changes in audiograms were noted in several patients. CI-973 concentrations were measured in plasma ultrafiltrate and urine by high-pressure liquid chromatography. The harmonic mean terminal half-life was 2.0 h. The mean CI-973 renal and nonrenal clearance values were 42.3 and 37.4 ml/min/m2, respectively. The mean recovery of CI-973 in urine was 53% of the administered dose. The mean ratio of CI-973 renal clearance to creatinine clearance was 0.92. Total clearance correlated with creatinine clearance (r2 = 0.63). A relationship between toxicity, expressed as the percentage of reduction in absolute granulocyte count, and area under the CI-973 plasma concentration-time curve was found in a subgroup of "good-risk" patients. This relationship, described well by a sigmoidal Emax pharmacodynamic model, did not hold for patients with extensive prior therapy or poor performance status. A model for toxicity prediction based on dose and creatinine clearance has been derived and will be validated in future studies. The recommended Phase II dose of CI-973 is 30 mg/m2/day for 5 days.
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PMID:Phase I and pharmacokinetic study of the novel platinum analogue CI-973 on a 5-daily dose schedule. 145 62

Eleven patients with testicular cancer, either relapsing after or refractory to cisplatin-based chemotherapy, underwent salvage chemotherapy with high-dose carboplatin (800 mg/m2 on day 1) and high-dose etoposide (500 mg/m2 on days 1, 3 and 5). A total of 21 courses were administered. The major toxicity consisted of profound myelosuppression. There were two toxic deaths, both caused by infection during neutropenia. Bone marrow recovery was usually complete around day 26 (range 19-129). Other toxicities included mild mucositis, nausea and vomiting, and alopecia. No significant neurotoxicity or hearing loss were observed and only one patient had a moderate decrease in renal function. Nine of ten evaluable patients responded, with one complete remission, 6 partial remissions with normalization of tumor markers, and two partial remissions with over one log decrease of tumor markers. The duration of these remissions was not evaluable, since only three evaluable and responding patients did not receive additional therapy after HD-CE. All three relapsed after discontinuing chemotherapy. HD-CE has activity in relapsing or refractory testicular cancer and can be administered without bone marrow support. The regimen may thus be suitable to be used as a remission induction regimen prior to consolidation with intensive chemotherapy and autologous bone marrow transplantation.
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PMID:Feasibility study of high-dose carboplatin and etoposide in the salvage treatment of testicular cancer. 149 65


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