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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2008-4-16
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pubmed:abstractText |
The pharmacokinetics (PK) and pharmacodynamics (PD) of metronomic irinotecan have not been studied in cancer patients. The aim of the study is to investigate the PK/PD profile of irinotecan/SN-38 administered by metronomic schedule. Twenty chemotherapy-refractory or chemotherapy-resistant patients with metastatic colorectal carcinoma were enrolled. Irinotecan was infused continuously as follows: irinotecan 1.4 mg m(-2) day(-1) (n=7), 2.8 mg m(-2) day(-1) (n=5) and 4.2 mg m(-2) day(-1) (n=8). Drug levels were examined by HPLC, whereas ELISAs and real-time RT-PCR were used, respectively, for the measurement of plasma levels and gene expression in peripheral blood mononuclear cells of vascular endothelial growth factor/thrombospondin-1. Pharmacokinetic analysis demonstrated that the steady-state levels (C(ss)) of SN-38 were between 1 and 3.3 ng ml(-1). From a PD point of view, higher thrombospondin-1 (TSP-1) plasma levels (153.4+/-30.1 and 130.4+/-9.2% at day 49 vs pretreatment values at 1.4 and 2.8 mg m(-2) day(-1) dose levels, respectively) and increased gene expression in PBMC were found during the metronomic irinotecan infusion, especially at the lower doses. Four patients (20%) obtained a stable disease (median 3.9 months) despite progressing during previous standard irinotecan schedule. Toxicities >grade 1 were not observed. Metronomic irinotecan administration is very well tolerated and induces an increase of gene expression and plasma concentration of TSP-1 at low plasma SN-38 concentrations.
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pubmed:commentsCorrections |
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18362940-18165643
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1532-1827
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pubmed:author |
pubmed-author:AllegriniGG,
pubmed-author:BarlettaM TMT,
pubmed-author:BocciGG,
pubmed-author:CernáAA,
pubmed-author:DanesiRR,
pubmed-author:Del TaccaMM,
pubmed-author:Di PaoloAA,
pubmed-author:FalconeAA,
pubmed-author:FioravantiAA,
pubmed-author:KerbelR SRS,
pubmed-author:LoupakisFF,
pubmed-author:MasiGG,
pubmed-author:OrlandiPP
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1312-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18362940-Aged,
pubmed-meshheading:18362940-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:18362940-Camptothecin,
pubmed-meshheading:18362940-Colorectal Neoplasms,
pubmed-meshheading:18362940-Female,
pubmed-meshheading:18362940-Granulocyte Colony-Stimulating Factor,
pubmed-meshheading:18362940-Humans,
pubmed-meshheading:18362940-Male,
pubmed-meshheading:18362940-Middle Aged,
pubmed-meshheading:18362940-Thrombospondin 1,
pubmed-meshheading:18362940-Vascular Endothelial Growth Factor A
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pubmed:year |
2008
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pubmed:articleTitle |
A pharmacokinetic and pharmacodynamic study on metronomic irinotecan in metastatic colorectal cancer patients.
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pubmed:affiliation |
Division of Medical Oncology, General Hospital of Livorno, Department of Oncology, University of Pisa, Pisa, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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