Abstract:
PURPOSE:The aromatase inhibitor, letrozole, is being investigated in experimental animal models as a novel treatment for high-grade gliomas (HGGs). To facilitate optimal dosing for such studies, we evaluated the plasma and brain pharmacokinetics (PK) of letrozole in NOD-scid gamma (NSG) mice, which are frequently employed for assessing efficacy against patient-derived tumor cells. Furthermore, we evaluated the potential PK interactions between letrozole and temozolomide (TMZ) in Sprague-Dawley rats. METHODS:NSG mice were administered letrozole (8 mg/kg; i.p) as a single or multiple dose (b.i.d, 10 days). Brain tissue and blood samples were collected over 24 h. Letrozole and TMZ interaction study employed jugular vein-cannulated rats (three groups; TMZ alone, letrozole alone and TMZ + letrozole). Intracerebral microdialysis was performed for brain extracellular fluid (ECF) collection simultaneously with venous blood sampling. Drug levels were measured employing HPLC and PK analysis was conducted using Phoenix WinNonlin®. RESULTS:In NSG mice, peak plasma and brain tissue letrozole concentrations (Cmax) were 3-4 and 0.8-0.9 µg/ml, respectively. The elimination half-life was 2.6 h with minimal accumulation following multiple dosing. In the drug interaction study, no PK changes were evident when TMZ and letrozole were given in combination. For instance, peak plasma and brain ECF TMZ levels when given alone were 14.7 ± 1.1 and 4.6 ± 0.6 µg/ml, respectively, and 12.6 ± 2.4 and 3.4 ± 0.8 µg/ml, respectively, when given with letrozole. CONCLUSIONS:These results will guide the optimization of dosing regimen for further development of letrozole for HGG treatment.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Arora P,Adams CH,Gudelsky G,DasGupta B,Desai PBdoi
10.1007/s00280-018-3705-6subject
Has Abstractpub_date
2019-01-01 00:00:00pages
81-89issue
1eissn
0344-5704issn
1432-0843pii
10.1007/s00280-018-3705-6journal_volume
83pub_type
杂志文章abstract:PURPOSE:The purpose of this article is to report the first case of markedly increased anticoagulant activity of warfarin when used in combination with doxifluridine, given as a replacement for capecitabine. METHODS:International normalized ratio (INR) of a 73-year-old female patient receiving warfarin was increased af...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1249-5
更新日期:2010-10-01 00:00:00
abstract:PURPOSE:Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine k...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2668-5
更新日期:2015-03-01 00:00:00
abstract:PURPOSE:To evaluate the plasma protein binding and pharmacokinetics of prednisolone during therapeutic use in children with acute lymphoblastic leukemia (ALL) using the population approach. METHODS:A two-compartment pharmacokinetic model was used to describe data from 23 children with ALL (aged 2-15 years). Prednisolo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0602-3
更新日期:2003-06-01 00:00:00
abstract:PURPOSE:Fludarabine is a renally excreted agent that is an effective treatment for chronic lymphocytic leukemia (CLL), a disease predominantly of the elderly. We sought to determine whether age, renal function or pretreatment hematologic status predicted toxicity of fludarabine treatment for CLL. METHODS:We evaluated ...
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/s00280-002-0443-5
更新日期:2002-07-01 00:00:00
abstract:PURPOSE:Midostaurin (PKC412) is a multitargeted tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 receptor (FLT3), c-KIT, and other receptors. Midostaurin is active in patients with acute myeloid leukemia and systemic mastocytosis. Although no substantive risk for cardiac abnormalities has been observed with mido...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-012-1825-y
更新日期:2012-05-01 00:00:00
abstract::The purpose of this study was to examine the efficacy of a combination treatment of sequential irinotecan and doxifluridine, an intermediate of capecitabine, evaluated by the response rate and safety in patients with metastatic colorectal cancer. In all, 60 metastatic colorectal cancer patients with measurable disease...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00280-007-0471-2
更新日期:2008-02-01 00:00:00
abstract::OSI-7836 (4'-thio-beta-D-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0844-8
更新日期:2005-03-01 00:00:00
abstract::To enable the treatment of hepatic metastasis with higher, theoretically more effective, doses of systemically toxic anticancer drugs, an isolated liver perfusion (ILP) technique was developed in WAG/Ola rats. First, in a toxicity study the maximally tolerated dose (MTD) of mitomycin C (MMC) was determined for a 25-mi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689698
更新日期:1991-01-01 00:00:00
abstract::D-3-Azido-3-deoxy-myo-inositol (3AMI) is an inhibitor of the growth of v-sis-transformed NIH 3T3 cells but not of wild-type NIH 3T3 cells, whose effects may be mediated through the phosphatidylinositol-3'-kinase pathway. We studied some properties of the cellular pharmacology of 3AMI using high-specific-activity [3H]-...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686287
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS:Tumors f...
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/s00280-018-3667-8
更新日期:2018-10-01 00:00:00
abstract:PURPOSE:We assessed the clinical efficacy and safety of mitoxantrone hydrochloride which has been used as an anticancer drug in our hospital to treat breast cancer patients since 1993. METHODS:A group of 23 patients with breast cancer were given one course of the following regimen every 3 weeks: mitoxantrone hydrochlo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0586-z
更新日期:2003-07-01 00:00:00
abstract::The interactions of cisplatin, 5-fluorouracil, doxorubicin, mitomycin, carmustine (BCNU), cyclophosphamide, methotrexate and thio-TEPA were assessed at three neurotransmitter receptor binding sites. Each drug was inactive at concentrations as high as 10(-4) M in displacing the specific binding of 3H-spiperone to dopam...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254564
更新日期:1987-01-01 00:00:00
abstract::We propose a mathematical model that takes into account a classical maximum tolerated dose (MTD) chemotherapy regimen (whose primary targets are the tumor cells) as well as a metronomic chemotherapy regimen (whose primary targets are the tumor endothelial cells) for the administration of temozolomide (Temodal(®)) in o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2095-z
更新日期:2013-04-01 00:00:00
abstract::Increasing the expression of human multidrug resistance (MDR) 1 gene in bone marrow cells to prevent or circumvent bone morrow toxicity from chemotherapy agent is a high priority of dose intensification protocols. In this study, we have used a tumor-bearing model to investigate the chemoprotection effect of MDR1 gene ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0144-y
更新日期:2006-07-01 00:00:00
abstract:PURPOSE:Since there is a growing interest in preclinical research on interactions between radiation and cytotoxic agents, this study focused on the development of an alternative to the very laborious clonogenic assay (CA). METHODS:The colorimetric sulforhodamine B (SRB) assay was compared to the clonogenic assay for r...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0557-9
更新日期:2003-03-01 00:00:00
abstract::The cytotoxic action of two morpholino anthracyclines, methoxymorpholino anthracycline (MRA-MT, FCE 23,762) and cyanomorpholino anthracycline (MRA-CN), was compared with the cytotoxicity of doxorubicin (DOX), the topoisomerase II inhibitor etoposide (VP-16), the topoisomerase I inhibitor camptothecin, methotrexate, an...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689457
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To compare the protective effect of dexrazoxane (DRZ) against cardiotoxicity induced by doxorubicin (DXR) and mitoxantrone (MTX). METHODS:Adult male spontaneously hypertensive rats (SHR) were treated with 1 mg/kg DXR (i.v.) or 0.5 mg/kg MTX (i.v.), either alone or 30 min after 25 mg/kg DRZ (i.p.) weekly for up...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100348
更新日期:2001-10-01 00:00:00
abstract:PURPOSE:This study evaluated the tolerability, pharmacokinetics, and preliminary antitumor activity of EZN-2208, a water-soluble poly(ethylene) glycol conjugate of SN38. METHODS:Patients with advanced malignancies were enrolled in dose-escalating cohorts (3 + 3 design). EZN-2208 was administered as a 1-h intravenous i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-013-2149-2
更新日期:2013-06-01 00:00:00
abstract:PURPOSE:D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050793
更新日期:1998-01-01 00:00:00
abstract::Two studies were carried out (A and B) in order to assess the effectiveness of ifosfamide administered with mesna (IFO/M) in the treatment of small cell lung cancer. The first study (A) was a cross-over study; the second (B) was a randomized trial, and in B IFO/M was evaluated earlier in the course of the disease. IFO...
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/BF00647447
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on bevacizumab pharmacokinetics. METHODS:Rich and sparse bevacizumab serum concentrations were collected from Phase I through IV studies in early a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3079-6
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in reducing 5-fluorouracil (FUra) host-toxicity and enhancing its chemotherapeutic efficacy against human colon tumors. PTAU is a potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0213-x
更新日期:2006-11-01 00:00:00
abstract::Sparsomycin is a cytotoxic drug exhibiting a broad spectrum of in vitro activity against murine tumors and many tumor cell lines. It also appears to be a potent stimulator of the antitumor activity of cisplatin against L1210 leukemia in vivo. However, because of its toxicity, the antitumor activity of sparsomycin on m...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00253964
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:To gain a better understanding of the impact of postprogression survival (PPS) and post-trial anticancer therapy on overall survival (OS) in first-line pancreatic cancer patients. METHODS:A literature search identified 54 randomized trials, focusing on gemcitabine monotherapy to eliminate effects of heterogene...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-017-3263-3
更新日期:2017-03-01 00:00:00
abstract:PURPOSE:Imatinib is an inhibitor of the Bcr-Abl tyrosine kinase; however, resistance is common. Flavopiridol, a cyclin-dependent kinase (CDK) inhibitor, down-regulates short-lived anti-apoptotic proteins via inhibition of transcription. In preclinical studies, flavopiridol synergizes with imatinib to induce apoptosis. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1839-5
更新日期:2012-06-01 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::Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-F...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686944
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:As a follow-up to our previous findings that platinum drugs induce a key enzyme in polyamine catabolism, gene expression profiling and mathematical modeling were used to define the effects of cisplatin and oxaliplatin on the expression of polyamine metabolic pathway genes in A2780 human ovarian carcinoma cells....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0325-3
更新日期:2007-05-01 00:00:00
abstract:PURPOSE:Defective expression of the mismatch repair protein MSH3 is frequently detected in colon cancer, and down-regulation of its expression was found to decrease sensitivity to platinum compounds or poly(ADP-ribose) polymerase inhibitors (PARPi) monotherapy. We have investigated whether MSH3 transfection in MSH3-def...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2175-0
更新日期:2013-07-01 00:00:00
abstract::Intravenous (i.v.) administration of sodium thiosulfate reduces the toxicity of cis-diamminedichloroplatinum (II) (CDDP). This effect, which allows the use of increased CDDP doses, has been exploited clinically in the intraperitoneal (i.p.) treatment of intraabdominal tumors. Recently, attempts have been made to treat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257358
更新日期:1988-01-01 00:00:00