Abstract:
PURPOSE:Cyclosporine A (CyA) is able to inhibit P-glycoprotein (P-gp) and to increase cytotoxicity of some anticancer drugs, including etoposide. However, the effect of CyA on the distribution of etoposide in normal tissues, which could affect their toxicity, has not been studied extensively. The purpose of this study was to investigate the effect of CyA on the pharmacokinetics and tissue distribution of etoposide in rats. METHODS:Etoposide was administered as an i.v. bolus injection (3 mg) or as a constant-rate i.v. infusion (8 mg/h) 1 h after the beginning of infusion of CyA or saline. Animals were killed 1 h after the bolus administration or after the beginning of infusion of etoposide, and plasma and tissue (testicle, muscle, heart, lung, spleen, kidney, liver, colon, and intestine) concentrations of etoposide, blood concentrations of CyA were determined. All analyses were performed by HPLC. RESULTS:Infusion of CyA (1 mg/h) in rats treated with an i.v. bolus of etoposide caused a decrease in the plasma clearance (5.4+/-2.1 vs 9.3+/-2.4 ml/min), and an increase in plasma and tissue concentrations of etoposide, but the tissue-to-plasma concentration ratios of etoposide were not affected. When etoposide was infused at a constant rate to reach a steady-state plasma level, coinfusion of CyA (10 mg/h) also caused a decrease in the plasma clearance (4.8+/-1.5 vs 9.8+/-4.7 ml/min), and an increase in plasma and tissue concentrations of etoposide. Only lung and spleen showed tissue-to-plasma ratios of etoposide significantly higher than obtained in rats coinfused with saline, but the differences were small. CONCLUSIONS:The higher tissue concentrations of etoposide caused by CyA administration were mainly a direct consequence of the higher plasma concentration resulting from a decrease in the clearance of etoposide rather than a consequence of changes in the tissue distribution of etoposide. Extrapolation of the results obtained in rats to clinical practice suggests that the coadministration of etoposide and CyA would not lead to an increase in the toxicity of etoposide if the dose were decreased in the same proportion as clearance of etoposide is decreased by CyA administration.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Cárcel-Trullols J,Torres-Molina F,Araico A,Saadeddin A,Peris JEdoi
10.1007/s00280-004-0784-3keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
153-60issue
2eissn
0344-5704issn
1432-0843journal_volume
54pub_type
杂志文章abstract:PURPOSE:RSR13, 2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methylpropanoic acid monosodium salt, allosterically modifies hemoglobin to increase tumor pO(2), increases the effect of radiation in animal tumor models, and is in phase III clinical trials as an adjuvant to radiotherapy. Cisplatin and carboplat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0715-8
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVE:SDX-101 is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac, and has anti-tumour activity in chronic lymphocytic leukaemia (CLL). SDX-308 and SDX-309 are more potent, structurally related indole-pyran analogues of SDX-101. The current study was performed to i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0400-9
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:Everolimus is a standard treatment option for advanced pancreatic neuroendocrine tumors (pNETs). This multicenter study evaluated the efficacy and safety of everolimus in low and intermediate grade advanced pNETs. METHODS:Tumors were graded according to the World Health Organization 2010 classification system....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-017-3421-7
更新日期:2017-10-01 00:00:00
abstract:PURPOSE:Standardized enumeration of CEC counts is required to minimize variability and allow cross-studies comparisons. The purpose of this paper is to identify CEC threshold proposal, by CellSearch system, for determining response to bevacizumab-based chemotherapy in metastatic colorectal cancer. METHODS:From July 20...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1543-2
更新日期:2011-09-01 00:00:00
abstract::Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin polymers, increasing the fraction of cells in the G2 or M phase of the cell cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10 microM taxol i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686187
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:Thyroid cancers with unsatisfactory curative effect nowadays are the most common malignant tumors of the endocrine system. Apoptosis evasion, a hallmark of cancer, has driven the search of stimulating novel cell death way in cancer therapy. This review aims to explore the relationship between autophagy and thyr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-013-2363-y
更新日期:2014-03-01 00:00:00
abstract::In five cancer patients we have determined the pharmacokinetics of 4'-deoxydoxorubicin (4'-DOX), its alcoholic metabolite 4'-deoxydoxorubicinol and the occurrence of circulating 7-deoxyaglycone metabolites. The 7-deoxyaglycone of the alcohol metabolite, the major aglycone of Adriamycin (ADR) present in man, was not de...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00570499
更新日期:1987-01-01 00:00:00
abstract::1-Hexylcarbamoyl-5-fluorouracil (HCFU) and its parent compound 5-fluorouracil (5-FU) were tested PO for antitumor activity against mouse colon adenocarcinoma 26 (colon 26), colon adenocarcinoma 38 (colon 38), and Lewis lung carcinoma. The drugs were given orally at 2--4 days intervals for a total of ten doses. 5-FU wa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254027
更新日期:1980-01-01 00:00:00
abstract::Unfortunately, the online published article has error in Figure 4. The correct Figure 4 is given here. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,已发布勘误
doi:10.1007/s00280-018-3590-z
更新日期:2018-06-01 00:00:00
abstract:PURPOSE:Our study was designed to evaluate the efficacy and safety of everolimus in patients with pre-treated metastatic gastric and esophagus cancers in a US-based population focusing on biomarker correlation. METHODS:Patients with advanced upper GI adenocarcinomas who progressed after 1-2 prior regimens received eve...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-015-2744-5
更新日期:2015-07-01 00:00:00
abstract::Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirub...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00685824
更新日期:1991-01-01 00:00:00
abstract::In recent years significant progress in the understanding of the immune biology of melanoma has evolved from the identification of melanoma antigens (MAs) recognized by T cells. MAs consist of intracellular proteins that are expressed on the surface of cancer cells in association with human leukocyte antigen (HLA) cla...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/pl00014052
更新日期:2000-01-01 00:00:00
abstract::This prospective, randomized, nonblind study comparing the antiemetic effectiveness of high-dose IV metoclopramide and high-dose IV dexamethasone was performed in 78 advanced cancer patients. Chemotherapeutic treatment consisted in cisplatin at a high-dose (120 mg/m2) (HD-CDDP) and at a low-dose (LD-CDDP), either alon...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00299870
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Cediranib (RECENTIN™) is an oral, highly potent VEGF inhibitor. This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers. METHODS:Si...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s00280-010-1534-3
更新日期:2011-09-01 00:00:00
abstract::The pharmacokinetics of hexamethylmelamine (HMM) and its first metabolite (hydroxymethylpentamethylmelamine: HMPMM) following IP bolus dose of 200 mg/kg were studied in mice. The drug concentrations were determined by a sensitive reversed-phase HPLC assay. Thus, for the first time, HMM major hydroxylated and demethyla...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00273391
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Capecitabine and S-1 are orally administered fluoropyrimidine anticancer drugs widely used to treat gastrointestinal cancer. While anticoagulant therapy for cancer patients is recommended, many studies have shown that the effects of warfarin are enhanced by its interaction with fluoropyrimidine. We investigated...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3080-0
更新日期:2016-08-01 00:00:00
abstract::The pharmacokinetics of pentamethylmelamine (PMM) have been investigated in mouse (Balb C-, CBA/LAC, nude), rat (Wistar), and man. In all three species, PMM was extensively demethylated to N2,N2,N4,N6-tetramethylmelamine and N2,N4,N6-trimethylmelamine, although marked species differences in the rate of metabolism were...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00292880
更新日期:1982-01-01 00:00:00
abstract::The intra-cellular uptake of the weakly basic radiosensitiser pimonidazole (PIMO) was determined as a function of the pigmentation of Na11+ human melanotic melanoma cells in vitro. Two experimental conditions were considered: exponentially growing cells (Exp.) and plateau-phase cells (PI.). The melanin content of Na11...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685671
更新日期:1993-01-01 00:00:00
abstract::We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-009-1217-0
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:The docetaxel/cisplatin (DC) combination is an active regimen against advanced/metastatic non-small-cell lung cancer (NSCLC), and bevacizumab (B) improves the efficacy of frontline chemotherapy. This phase II study was designed in order to explore the efficacy and safety of DCB regiment in this setting. MET...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2037-1
更新日期:2013-03-01 00:00:00
abstract:PURPOSE:The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon can...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002800050576
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:To assess the safety of the association of radiotherapy (RT) and systemic treatments for patients with metastatic malignant melanoma (mMM). METHODS:A retrospective analysis included consecutive patients treated with palliative RT, and at least one line of systemic therapy for mMM between 2001 and 2016. Treatme...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03806-5
更新日期:2019-05-01 00:00:00
abstract::BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1-2 microM, whereas they showed hardly any synergistic effect in the parental cell line ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257444
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:To determine the efficacy and safety of the combination therapy with docetaxel and cisplatin (CDDP) at low doses in elderly patients with advanced NSCLC. PATIENTS AND METHODS:A total of 42 patients aged > or =70 years with previously untreated advanced NSCLC received docetaxel 75 mg/m(2) plus CDDP 50 mg/m(2) o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-008-0749-z
更新日期:2009-02-01 00:00:00
abstract:PURPOSE:This is a phase-I study of gefitinib in combination with temozolomide in patients with gliomas. The goal of the study was to define the maximum tolerated dose (MTD) and to characterize the pharmacokinetics of gefitinib when combined with temozolomide. PATIENTS AND METHODS:Patients were stratified according to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0556-y
更新日期:2008-05-01 00:00:00
abstract::A model incorporating recent information regarding the specificity of a high-performance liquid chromatographic assay for "active" platinum in plasma ultrafiltrate, and the concept of mobile and fixed metabolites, was developed for cancer patients treated with cisplatin. Model parameters were determined using plasma a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00252955
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:In gemcitabine-pretreated pancreatic cancer, salvage chemotherapy has not been established, and the prognostic factors are not completely known. The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) in patients with gemcitabin...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-011-1584-1
更新日期:2011-10-01 00:00:00
abstract:PURPOSE:This phase I study was undertaken to evaluate the safety and tolerability of prolonged infusional etoposide, and to evaluate its pharmacokinetic/pharmacodynamic profile in patients with advanced cancer. METHODS:A group of 17 patients received a 7-day infusion of etoposide (schedule A) every 21 days at doses fr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050511
更新日期:1996-01-01 00:00:00
abstract::Purified human leukocyte interferon produced by recombinant techniques (IFN-alpha A) was tested in vitro with chemotherapeutic drugs, vinblastine (VLB), vincristine (VCR), vindesine (VDS), vinzolidine (VZL), cis-platinum (PLAT), doxorubicin (DOXO), etoposide (VP-16), and melphalan (MEL). The activity of these agents a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00255753
更新日期:1983-01-01 00:00:00
abstract::A total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were greater than 70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was greater than or equal to 70% for 40 patients. Malignancies were hematopoietic ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00687328
更新日期:1991-01-01 00:00:00