Abstract:
PURPOSE:Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients. METHOD:This article describes a method for the quantitative determination of decitabine triphosphate in PBMCs using liquid chromatography coupled to tandem mass spectrometry. The method was applied to ex vivo incubated whole blood samples and samples from three patients receiving prolonged low-dose decitabine treatment. RESULTS:We successfully quantitated decitabine triphosphate in PBMCs. Considerable levels were detected in PBMCs from two patients that responded well to therapy, whereas only low levels were present in a non-responding patient. Moreover, the data show that, in contrast to plasma decitabine, intracellular decitabine triphosphate accumulates during a treatment cycle of nine infusions at a dose of 15 mg/m(2). CONCLUSIONS:The results suggest a relationship between decitabine triphosphate levels and response to therapy. Based on the observed accumulation of decitabine triphosphate during a treatment cycle, a less intensive dose scheme could be feasible.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Jansen RS,Rosing H,Wijermans PW,Keizer RJ,Schellens JH,Beijnen JHdoi
10.1007/s00280-012-1850-xsubject
Has Abstractpub_date
2012-06-01 00:00:00pages
1457-66issue
6eissn
0344-5704issn
1432-0843journal_volume
69pub_type
杂志文章abstract:BACKGROUND:Cetuximab and panitumumab are chimeric and fully human monoclonal antibodies, respectively, against epidermal growth factor receptor used in the treatment of metastatic colorectal cancer (mCRC). Incidence of documented infusion reaction (IR) is more common with cetuximab (all grades [g]: 15-21%, g 3/4: 2-5%)...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1009-6
更新日期:2009-12-01 00:00:00
abstract:PURPOSE:4'-Thio-β-D-arabinofuranosylcytosine (4'-thio-ara-C), which has shown a broad spectrum of antitumor activity against human tumor systems in mice and is undergoing clinical trials, was evaluated for cross-resistance to seven clinical agents in order to identify potentially useful guides for patient selection for...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1498-3
更新日期:2011-08-01 00:00:00
abstract::The antimetabolite 1-beta-D-arabinofuranosyl-cytosine (ara-C) has proven to be one of the most effective agents available for the treatment of acute leukemia. While ara-C has been implicated as a potent inhibitor of mammalian cell DNA replication, the specific mechanism by which ara-C kills cells is not known. In this...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050496
更新日期:1996-01-01 00:00:00
abstract::Valinomycin is a depsipeptide antibiotic that selectively translocates potassium ion across biologic membranes. This drug has been reported to display antitumor effects, but its use has been limited by its extreme toxicity. However, its incorporation into lipid vesicles (liposomes) has resulted in a reduction in toxic...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00267946
更新日期:1989-01-01 00:00:00
abstract::Anaesthetized rabbits were infused with methotrexate (MTX; 30 micrograms x kg-1 x min-1) for 4 h. Constant plasma concentrations of MTX and its main metabolite 7-hydroxymethotrexate (7-OH-MTX) were achieved 40-60 min after the start of the infusion. In all, 50% of the infused MTX was eliminated by the kidney; another ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897260
更新日期:1990-01-01 00:00:00
abstract::To evaluate the antiemetic efficacy of high-dose methylprednisolone (MP) in previously untreated cancer patients receiving cisplatin (CPDD) for the first time, we performed a randomized double blind study. MP or a placebo (PLB) was administered six times during each course of chemotherapy. The first dose was 500 mg an...
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/BF00258123
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVE:Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in brea...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-020-04030-2
更新日期:2020-04-01 00:00:00
abstract::To predict the clinical effect on leukemic disease of a combination regimen developed to circumvent multidrug resistance (MDR), we tested various antitumor agents in the presence and absence of AHC-52, a sensitizing agent for multidrug-resistant cells, in the i.v.-i.v. model of murine leukemia. In this model system, s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689959
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer. METHODS:A total...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3067-x
更新日期:2016-07-01 00:00:00
abstract:INTRODUCTION:Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to p...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3455-x
更新日期:2018-01-01 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:OBJECTIVE:The aim of this study was to evaluate the efficacy and toxicities of liposome-paclitaxel and carboplatin concurrent with radiotherapy for locally advanced lung squamous cell carcinoma (LSCC). METHODS:The clinical data of 38 patients with locally advanced LSCC treated with liposome-paclitaxel based concurrent...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3640-6
更新日期:2018-09-01 00:00:00
abstract::Infusion of 5'-dFUrd (2.0-3.0 g/m2 over 1 h on days 1-5 every 3rd week) resulted in one partial response in 21 patients with advanced and progressing colorectal cancer. No patient had received chemotherapy before the 5'-dFUrd trial. Hematological and gastrointestinal toxicity were generally mild. In 4 patients periphe...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257528
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral rubitecan administered in a daily times five schedule. METHODS:Concentration-time data of rubitecan and 9-A...
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/s00280-002-0516-5
更新日期:2002-12-01 00:00:00
abstract::The selective Aurora-A kinase inhibitor MLN8237 is in clinical trials for hematologic malignancies, ovarian cancer and other solid tumors. We previously showed that MLN8237 is potently antiproliferative toward standard monolayer-cultured glioblastoma cells. We have now investigated the effect of MLN8237 with and witho...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2430-z
更新日期:2014-05-01 00:00:00
abstract:PURPOSE:Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of capecitabine. METHODS:We enrolled postoperativ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04087-z
更新日期:2020-06-01 00:00:00
abstract::The present study deals with the influence of some bis(eta 5-cyclopentadienyl)titanium(IV) (titanocene) complexes, mainly represented by titanocene dichloride, on the development of several human gastrointestinal (GI) carcinomas (one stomach, seven colon, four sigmoid, and two rectal adenocarcinomas), all xenografted ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00451646
更新日期:1989-01-01 00:00:00
abstract::Levels of radioactivity and total anthracycline fluorescence in tissues of A/JAX mice were compared 1 h after IV administration of unlabeled or [14C]-labeled AD 32 (50 mg/kg). Highest levels of both fluorescence and radioactivity were found in the small intestine (including contents) and liver, a result consistent wit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00253006
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:To differentiate the antagonistic and agonistic effect of toremifene at the level of the hypothalamus-hypophysis axis a leutinizing hormone-releasing hormone (LHRH) test was performed during a phase II clinical trial. METHODS:In 15 postmenopausal patients with advanced breast cancer, follicle-stimulating hormo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050811
更新日期:1998-01-01 00:00:00
abstract::Relationships between in vitro chemosensitivity and cell nuclear DNA content were investigated in malignant cells from 41 patients exhibiting advanced gastric carcinoma. The chemosensitivity was evaluated by measuring the succinate dehydrogenase (SD) activity in drug-exposed cancer cells and the DNA content was micros...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686250
更新日期:1992-01-01 00:00:00
abstract::Recent studies in human bone-marrow culture and healthy human volunteers suggest that lenograstim [glycosylated, recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in Chinese hamster ovary (CHO) cells] has greater in vivo potency than filgrastim [nonglycosylated, methionine-extended recombinan...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050570
更新日期:1997-01-01 00:00:00
abstract::We have developed and validated a selective analytical procedure, based on ion-exchange normal-phase liquid chromatography with fluorescence detection and liquid-liquid extraction, for the analysis of vinblastine (VBL) in biological matrices. The assay is suitable for the determination of the parent compound and its m...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686174
更新日期:1993-01-01 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::We have recently demonstrated that continuous-infusion (CI) 5-fluorouracil (FU) eradicates human colon carcinoma cells made resistant to bolus FU in vitro. In addition, in the same experimental system, the mechanisms of resistance to pulse and CI FU were found to be different. These observations led us to test the cli...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685339
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However, no standard treatment regimens have been established. This phase II study was designed to evaluate the efficacy and safety of a paclitaxel, cisplatin and 5-FU combination in metastatic and/...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-2020-x
更新日期:2013-02-01 00:00:00
abstract:PURPOSE:Chemosensitizers such as cyclosporin A can increase intracellular accumulation of chemotherapeutic agents such as Adriamycin in certain multidrug-resistant (MDR) cell lines with overexpression of P-glycoprotein. It is likely that, when combined with cyclosporin A, hyperthermia could increase membrane permeabili...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050033
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:Based on the preclinical evidence of topoisomerase I (Topo-1) upregulation by mitomycin C(MMC) and decreased NF-kappaB activation by celecoxib, we evaluated combinations of irinotecan/MMC and irinotecan/MMC/celecoxib in patients with advanced solid malignancies. PATIENTS-METHODS:Initially, patients received MM...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0826-3
更新日期:2009-05-01 00:00:00
abstract:PURPOSE:We reported the first case of phenytoin intoxication due to the concomitant use of phenytoin and TS-1, together with a review of the literature regarding the occurrence of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs such as fluorouracil (5-FU) and tegafur ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0621-6
更新日期:2008-08-01 00:00:00
abstract:PURPOSE:Dinaciclib inhibits cyclin-dependent kinases 1, 2, 5, and 9 with a better therapeutic index than flavopiridol in preclinical studies. This study assessed the activity of dinaciclib in acute leukemia both in the clinic and in vitro. METHODS:Adults with relapsed/refractory acute myeloid leukemia (n = 14) and acu...
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/s00280-013-2249-z
更新日期:2013-10-01 00:00:00
abstract::The stability of solutions of the antitumour antimetabolites, vinca alkaloids, podophyllotoxins, interferons, steroids and platinum drugs as well as maytansine, asparaginase, amsacrine, flavone-8-acetic acid, mitoguazone, and N-phosphonoacetyl-L-aspartate (PALA) is reviewed. Much of the published work has been done wi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00451642
更新日期:1989-01-01 00:00:00