Abstract：
PURPOSE:To evaluate whether celecoxib alters the conversion of gemcitabine into its active metabolite, difluorodeoxycytidine triphosphate (dFdCTP), in peripheral blood mononuclear cells (PBMCs). METHODS:Patients with advanced pancreatic cancer who had not received chemotherapy and had acceptable organ function were eligible for the study. The initial dose of gemcitabine was 750 mg/m(2) administered intravenously at a rate of 10 mg/m(2)/min on days 1, 8, and 15 every 4 weeks. Celecoxib was administered orally at 400 mg twice a day starting 2 days after the first dose of gemcitabine. Serial blood samples were taken during the first and second gemcitabine infusions and the cellular dFdCTP levels from PBMCs were analyzed. RESULTS:Five patients received gemcitabine at 750 mg/m(2) and six patients received it at 650 mg/m(2). Severe adverse events included neutropenia, thrombocytopenia, enteritis, and gastric perforation. Two patient died early during treatment. Cellular pharmacology studies showed that the conversion of gemcitabine into dFdCTP was not affected by celecoxib. CONCLUSION:Despite the increased clinical toxicities encountered with the combination, celecoxib did not alter the conversion of gemcitabine into its active metabolites in PBMCs. Gemcitabine 650 mg/m(2) infusion over 65 min on days 1, 8, and 15 every 4 weeks in combination with celecoxib at 400 mg twice a day was the dose recommended for further study.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Xiong HQ,Plunkett W,Wolff R,Du M,Lenzi R,Abbruzzese JLdoi
10.1007/s00280-004-0916-9keywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
559-64issue
6eissn
0344-5704issn
1432-0843journal_volume
55pub_type
临床试验,杂志文章abstract：:Saturable elimination of 5-FU is exhibited in rats during constant infusions. Over the range of 3-480 mg/m2/h, total-body clearance of 5-FU decreases from 600 ml/min/m2 to less than 90 ml/min/m2. Previously published values for catabolism of 5-FU by rat hepatocytes can be used to simulate the plasma concentrations of ...
journal_title：Cancer chemotherapy and pharmacology
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doi：10.1007/BF00434346
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
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abstract：:Leukemic cells from seven patients with acute nonlymphoblastic leukemia and granulocytes, and mononuclear cells from three healthy controls were isolated by centrifugation on metrozoate-dextran. The intracellular accumulation of both the free and DNA-bound forms of daunorubicin and doxorubicin was studied in vitro. Th...
journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
pub_type： 杂志文章
doi：10.1007/BF00257528
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journal_title：Cancer chemotherapy and pharmacology
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更新日期：2009-12-01 00:00:00
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journal_title：Cancer chemotherapy and pharmacology
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更新日期：2012-10-01 00:00:00
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journal_title：Cancer chemotherapy and pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00280-005-1011-6
更新日期：2005-12-01 00:00:00
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
pub_type： 临床试验,杂志文章
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
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journal_title：Cancer chemotherapy and pharmacology
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更新日期：2018-07-01 00:00:00
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