Abstract:
PURPOSE:Plitidepsin absorption, distribution, metabolism and excretion characteristics were investigated in a mass balance study, in which six patients received a 3-h intravenous infusion containing 7 mg 14C-plitidepsin with a maximum radioactivity of 100 µCi. METHODS:Blood samples were drawn and excreta were collected until less than 1% of the administered radioactivity was excreted per matrix for two consecutive days. Samples were pooled within-patients and between-patients and samples were screened for metabolites. Afterwards, metabolites were identified and quantified. Analysis was done using Liquid Chromatography linked to an Ion Trap Mass Spectrometer and offline Liquid Scintillation Counting (LC-Ion Trap MS-LSC). RESULTS:On average 4.5 and 62.4% of the administered dose was excreted via urine over the first 24 h and in faeces over 240 h, respectively. Most metabolites were found in faeces. CONCLUSION:Plitidepsin is extensively metabolised and it undergoes dealkylation (demethylation), oxidation, carbonyl reduction, and (internal) hydrolysis. The chemical formula of several metabolites was confirmed using high resolution mass data.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
van Andel L,Rosing H,Tibben MM,Lucas L,Lubomirov R,Avilés P,Francesch A,Fudio S,Gebretensae A,Hillebrand MJX,Schellens JHM,Beijnen JHdoi
10.1007/s00280-018-3637-1subject
Has Abstractpub_date
2018-09-01 00:00:00pages
441-455issue
3eissn
0344-5704issn
1432-0843pii
10.1007/s00280-018-3637-1journal_volume
82pub_type
杂志文章abstract:PURPOSE:To investigate the synergistic cytotoxicity of TRAIL in combination with chemotherapeutic agents in A549 cell lines, we systematically evaluated the cytotoxicity of TRAIL alone and TRAIL in combination with cisplatin, paclitaxel (Taxol) or actinomycin D in A549 cell lines in vitro and in vivo, and whether the s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0867-1
更新日期:2005-02-01 00:00:00
abstract:PURPOSE:To investigate whether coadministration of vindesine is a risk factor for acute kidney injury caused by high-dose methotrexate in patients with hematologic malignancies and identify its mechanism. METHODS:A retrospective analysis was conducted on 211 cycles of HD-MTX therapy in 178 patients with hematological ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03972-6
更新日期:2020-02-01 00:00:00
abstract:PURPOSE:5-Fluorouracil is the most commonly used drug for the treatment of colon cancer, yet clinical resistance to this drug is frequently observed in patients making this drug ineffective. Thus, identification of gene responsible for 5-FU resistance is of utmost importance. METHODS:Cellular cytotoxicity and expressi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2794-8
更新日期:2015-09-01 00:00:00
abstract::The value of estrogen receptor (ER) status in the prediction of tumor response to combination chemotherapy was retrospectively analyzed in breast cancer patients selected for prospective controlled trials of chemotherapy (85 with advanced disease and 256 with operable tumors). All patients were previously untreated wi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00255456
更新日期:1980-01-01 00:00:00
abstract::Use of cross-sectional imaging to identify whole-body lean soft-tissue mass has recently emerged as an attractive prognostic factor for chemotherapy toxicities. Beyond that, there is increasing interest in use of lean soft-tissue mass as a more accurate method for dosing chemotherapy, as compared to body surface area....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-018-3614-8
更新日期:2018-07-01 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:PURPOSE:This study was performed to evaluate the safety and determine the recommended dose (RD) of resminostat monotherapy, an oral histone deacetylase (HDAC) inhibitor, in Japanese patients with advanced solid tumors. METHODS:Resminostat was administered to patients with advanced solid tumors on a 14-day cycle consis...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2741-8
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular conte...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000208
更新日期:2001-03-01 00:00:00
abstract::The cytotoxic effects of ketoconazole, an antifungal agent known to have some activity against human prostate cancer, adrenal cancer, and male metastatic breast cancer, were evaluated using colony-growth and clonogenic assays in eight malignant cell lines. The cytotoxicity of ketoconazole showed a dose- and time-depen...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00264198
更新日期:1988-01-01 00:00:00
abstract::In the original article, corresponding author's given name and family name are flipped. It should be "Siqing Fu" rather than "Fu Siqing". ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 已发布勘误
doi:10.1007/s00280-016-3002-1
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:Although irinotecan monotherapy is often used in third-line treatment after the failure of taxanes in Japanese clinical practice, its survival benefit is still unclear. The aim of this study is to investigate the efficacy and safety of irinotecan monotherapy as third-line treatment. METHODS:Clinical data from ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3138-z
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND/AIMS:Treatment responses of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remain unacceptably low and treatment modalities are limited. We compared the efficacy and safety of sorafenib and hepatic arterial infusion chemotherapy (HAIC). METHODS:In this randomized, prospecti...
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/s00280-018-3638-0
更新日期:2018-09-01 00:00:00
abstract::Characterization of the pharmacokinetics of 2-FLAA has been completed in seven patients receiving 18 or 25 mg/m2 daily X 5 of 2-FLAMP over 30 min. Assuming 2-FLAMP was instantaneously converted to 2-FLAA, the plasma levels of 2-FLAA declined in a biexponential fashion. Computer fitting of the plasma concentration-time...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256699
更新日期:1986-01-01 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::We obtained evidence that the cytotoxic effect of 5-fluorouracil (5-FU) is augmented when the drug is given in combination with hyperthermia (HYP) and dipyridamole (DP). Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and HYP against B16 melanoma and human tumor cells in vitro as measured by the succi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685941
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Ifosfamide is a cornerstone of chemotherapy in bone and soft-tissue sarcoma. Results of pharmacokinetic studies indicate that the optimal schedule of ifosfamide should be repeated doses over several days. With the development of 5-day infusion devices, we developed and evaluated a 5-day infusion regimen of ifos...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-009-1054-1
更新日期:2010-02-01 00:00:00
abstract:PURPOSE:Oxaliplatin and satraplatin demonstrate activity against cisplatin-resistant tumor cells. Although the two platinum analogs are structurally-related, oxaliplatin is more active. Therefore, studies focusing on protein expression profiling were undertaken to identify the molecular mechanism for the difference in ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04085-1
更新日期:2020-06-01 00:00:00
abstract:PURPOSE:We designed a phase I/II trial of intraperitoneal (IP) docetaxel plus S-1 to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate its efficacy and safety in gastric cancer patients with peritoneal carcinomatosis (PC). METHODS:Patients with PC confirmed by laparoscopy or laparoto...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2122-0
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive tumour, but this sensitivity is not reflected in an impact on survival. The study of new drugs is therefore indicated. Pirarubicin (4'-O-tetrahydropyranyl-doxorubicin) has a higher preclinical index than doxorubicin, with low cardiotoxicity...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686275
更新日期:1994-01-01 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:BACKGROUND AND AIMS:oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-005-1024-1
更新日期:2005-12-01 00:00:00
abstract::Twenty-seven patients with liver metastases from colorectal carcinoma were treated with 5-fluorouracil, adriamycin, and mitomycin C (FAM) by hepatic artery infusion (HAI) every 2-3 months for a maximum of eight courses. Median survival for all patients was 22 months. Toxicity was acceptable and consisted in severe mye...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00269032
更新日期:1984-01-01 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::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::The 9L gliosarcoma growing subcutaneously in the hind leg of the Fisher 344 rat contains major areas of severe (< 5 mmHg) hypoxia, making up about 49% of the tumor. Intravenous administration of an ultrapurified polymerized bovine hemoglobin solution (8 ml/kg) along with normal air breathing reduces the percentage of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686024
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Inhibition of the mammalian target of rapamycin (mTOR), a regulator of hypoxia inducible factor (HIF), is an established therapy for advanced renal cell cancer (RCC). Inhibition of mTOR results in compensatory AKT activation, a likely resistance mechanism. We evaluated whether addition of the Akt inhibitor peri...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1684-y
更新日期:2012-01-01 00:00:00
abstract::Cultures of human colon carcinoma, HCT-8, were treated with millimolar concentrations of thymidine by different schedules designed to cytokinetically and biochemically modulate methotrexate (MTX) and 5-fluorouracil (FUra) toxicity. Thymidine (dThd)-synchronized HCT-8 cells monitored by flow cytofluorometry showed incr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254600
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:Capecitabine plus cisplatin (XP) is a standard therapy for metastatic gastric cancer (mGC). However, while results from previous phase III trials suggested that the cisplatin dosage should be reduced in Japanese patients, no clinical data exist to support this. Here, we conducted a multicenter study to evaluate...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-016-3204-6
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:Cytotoxic chemotherapy has been used to treat patients with metastatic colorectal cancer with limited success. Therefore novel chemotherapeutic approaches are needed. Based on encouraging preclinical data, there has been an interest in developing derivatives of butyrate as clinically applicable agents. The purp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-001-0390-6
更新日期:2002-01-01 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