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)

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

A reconstituted lipoprotein, containing human apolipoprotein A-I and phosphatidylcholine (1:200, molar ratio), referred to as ApoLipo, was used prophylactically in an endotoxin shock model in anesthetized rabbits. ApoLipo was administered at a dose of 75 mg protein/kg body weight 15 min before the beginning of a slow, continuous lipopolysaccharide (LPS, endotoxin) infusion (4.17 micrograms LPS/kg/hr). During the 6 hr LPS infusion, the Control-LPS group manifested a marked increase in serum tumor necrosis factor (TNF, peak value 7.82 [2.7-11.2] ng/ml at 1 hr), and many of the pathophysiologic sequelae of endotoxin shock, including hypotension (MAP: 59 +/- 7 mmHg) and metabolic acidosis (BE: -9.9 +/- 2.7) at 3 hr, and a severe neutropenia developed rapidly (PMN count: 5 +/- 3% of baseline at 30 min). In the ApoLipo treated group, serum TNF levels did not rise during the course of LPS infusion (0.1 [0.06-0.64] ng/ml at 1 hr). Hypotension (77 +/- 2 mmHg) and acidosis (-2.7 +/- 0.4) were also significantly attenuated, and the appearance of leukopenia was delayed by 1 hr (110 +/- 12% at 30 min, but 9 +/- 2% at 2 hr). Endotoxemia in the ApoLipo treated group was reduced in comparison to controls, albeit nonsignificantly. The infusion of the same dose of phosphatidylcholine without apoA-I was significantly less efficacious.
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PMID:A reconstituted, apolipoprotein A-I containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. 832 86

A 68-year-old female underwent radical mastectomy for left breast cancer in April, 1995. She was treated with conventional combination chemotherapy (CEF) before and after surgery as an adjuvant therapy. She was treated with oral tamoxifen (TAM) and/or medroxyprogesterone (MPA) and doxifluridine daily after surgery. In May, 1998, she was found to have developed a subcutaneous tumor of the head and skull-bone, and a meningeal metastasis. We treated her with 80 mg docetaxel (TXT) one time with radiation (total dose 50 Gy), and with 70 mg two times. After the combination therapy, she achieved partial remissions of the metastases and a decrease in serum CEA. Adverse reactions to TXT were grade 3 alopecia, grade 3 to 4 neutropenia, grade 2 to 3 stomatitis, and grade 2 diarrhea. All were tolerable and reversible. The combination therapy of radiation and TXT may be a good strategy for recurrent breast cancer.
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PMID:[A case of head metastases of breast cancer successfully treated with radiation therapy and docetaxel]. 1092 93

The chemotactic factor formyl-methionyl-leucyl-phenylalanine (FMLP) when injected in rabbits causes dose-dependent transient hypotension, as well as neutropenia, thrombocytopenia and a decrease in systemic vascular resistance, as previously shown. Since both FMLP and endotoxin are elaborated at sites of infection by certain bacteria, whether they act in concert to produce shock was examined. Animals were pretreated with 380 microg/kg of E. coli endotoxin, 24 hours before the infusion of 10(-9) moles FMLP and were compared with animals pretreated only with saline and administered FMLP. Within 3 min after FMLP, endotoxin-pretreated animals developed a significant fall in MAP (p < 0.001) and neutrophils (p < 0.001) compared to controls. Statistically significant lactic acidemia, with reduced HCO(-)3 levels also developed in the endotoxin-pretreated group after FMLP injection. These results indicate that endotoxin apparently induces a prepared state, thus facilitating the hemodynamic and cellular effects of FMLP in this model.
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PMID:Endotoxin augments hemodynamic and metabolic effects of formyl-methionyl-leucyl-phenylalanine (FMLP) in rabbits. 1735 18

Sotrastaurin, a novel protein-kinase-C inhibitor, blocks early T-cell activation. In this 12-month, Phase II study, de novo renal-transplant patients were randomized to sotrastaurin (200 mg b.i.d.) + standard-exposure tacrolimus (SET) or reduced-exposure tacrolimus (RET) (SET: n = 76; RET: n = 66), or control (SET + mycophenolic acid [MPA, 720 mg b.i.d.]; n = 74). In both sotrastaurin groups, patients were converted from tacrolimus to MPA after Month 3, achieving calcineurin inhibitor-free immunosuppression. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up). The key secondary endpoint was glomerular filtration rate (GFR). Composite efficacy failure rates were: 4.1%, 5.4% and 1.5% at Month 3 (preconversion) and 7.8%, 44.8% and 34.1% at study end in the control, sotrastaurin + SET and sotrastaurin + RET groups, respectively; these results led to premature study discontinuation. Median GFR at Month 6 was: 57.0, 53.0 and 60.0 mL/min/1.73 m(2), respectively. Study-drug discontinuations due to adverse events occurred in 16.2%, 18.4% and 12.1%, respectively. Leukopenia and neutropenia occurred more frequently preconversion in control versus sotrastaurin groups: 13.7%, 5.6%, and 4.6%; and 11.1%, 4.3% and 3.1%, respectively. The initial sotrastaurin + tacrolimus regimen was efficacious and well tolerated but the postconversion sotrastaurin + MPA regimen showed inadequate efficacy. Longer-term evaluation of sotrastaurin + tacrolimus is warranted.
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PMID:Sotrastaurin, a novel small molecule inhibiting protein kinase C: first clinical results in renal-transplant recipients. 2012 45

The optimal adjuvant treatment for gastric cancer remains controversial. We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen, in patients with high-risk gastric cancer, with that of the same chemotherapy plus radiation therapy (RT). In addition, we evaluated the prognostic and/or predictive value of a panel of molecular markers. Patients with histologically proven, radically resected gastric cancer, stage > or =T3 and/or N+ were randomized to 6 cycles of docetaxel with cisplatin, both at 75 mg/m2 every 3 weeks (arm A) or the same treatment with RT (arm B; 45 Gy). Due to excessive nausea and vomiting, cisplatin was substituted by carboplatin at AUC (area under the curve) of 5 after the first 45 patients (22 group A, 23 group B). The prognostic value of EGFR, ERCC1, HER2, MET/HGFR, MAP-Tau, and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays (TMAs). A total of 147 patients were randomized. After a median follow-up of 53.7 months, no differences in overall (OS) and disease-free survival (DFS) were found between the two arms. The most common grade 3/4 toxicities for arms A and B (excluding alopecia) were non-febrile neutropenia (11 and 17%, respectively), febrile neutropenia (9 and 7%) and diarrhea (7 and 4%, respectively). Patients with ERCC1 positive tumors had significantly longer median DFS (33.1 vs. 11.8 months, Wald P = 0.016) and OS (63.2 vs. 18.8 months, Wald P = 0.046). Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk, radically resected gastric cancer. However, the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded.
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PMID:A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. 2115 23