Abstract:
:Carboxypeptidase G2 (CPG2) is used when unexpected toxicity or renal failure occurs during high-dose methotrexate therapy. Leucovorin is also administered to antagonise the effects of methotrexate on purine anabolism. To investigate the effects of CPG2 on leucovorin rescue, we incubated the enzyme with both stereoisomers and analysed the degradation. A method for separating the stereoisomers of leucovorin, the internal standard aminopterin and the degradation products by capillary electrophoresis with 2.6-dimethyl-beta-cyclodextrin as a chiral selector has been developed. The active 6S-leucovorin is degraded much faster than the inactive 6R-isomer. The maximum observed degradation velocity was 31 microM/min for 6S-leucovorin and 20 microM/min for 6R-leucovorin, respectively, with an initial concentration of each stereoisomer of 250 microM. Similar results were obtained at lower concentrations of leucovorin isomers. Thus, the selectivity of CPG2 for methotrexate in comparison to leucovorin is not as high as anticipated in the literature as only the active 6S-leucovorin and not the mixture of the diastereomers should be taken into account. We conclude that the protective effects of leucovorin are antagonized by CPG2. Therefore, CPG2 should be administered to patients with caution.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Hempel G,Lingg R,Boos Jdoi
10.1007/s00280-004-0910-2keywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
347-353issue
4eissn
0344-5704issn
1432-0843pii
10.1007/s00280-004-0910-2journal_volume
55pub_type
杂志文章abstract::The purpose of this study was to determine long-term renal platinum excretion after chemotherapy with cisplatin. We examined urinary platinum concentrations in 23 men at 150-3022 days after anticancer treatment for testicular neoplasm. Spot urine samples were analyzed by voltammetry. This new, subtle method with a det...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685736
更新日期:1995-01-01 00:00:00
abstract::Fourteen new agents of natural products origin which are under development as antitumor agents at the National Cancer Institute are discussed with reference to their sources, structures, antitumor activity, current status, and future prospects as clinically effective agents. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254042
更新日期:1978-01-01 00:00:00
abstract::Equimolar doses of chlorambucil and melphalan (both 10 mg/kg) were administered i.v. to anesthetized rats, and the plasma and brain concentrations of chlorambucil, its metabolites 3,4-dehydrochlorambucil and phenylacetic mustard, and melphalan were determined by high-performance liquid chromatography from 5 to 240 min...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262729
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (U...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-006-0377-4
更新日期:2007-08-01 00:00:00
abstract::New active drugs are needed for the treatment of primary brain tumors in both children and adults. S16020 is a cytotoxic olivacine derivative that inhibits topoisomerase II. The aim of the study was to determine its antitumor activity in athymic mice bearing subcutaneous medulloblastoma (IGRM33, 34, 57) and glioblasto...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0584-1
更新日期:2003-05-01 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::Physicochemical properties of two types of adriamycin preparation, suspensions and emulsions prepared for i.a. chemotherapy of hepatocellular carcinoma, were investigated. A suspension was prepared by dispersing adriamycin directly into the lipid contrast medium, Lipiodol, whereas an emulsion was obtained by emulsifyi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00451648
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary. METHODS:The effects of 6-gingerol on ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03999-9
更新日期:2020-02-01 00:00:00
abstract::A B16 melanoma cell line in which resistance to doxorubicin (Dx) had been induced by in vitro exposure to the drug, was found not to be cross-resistant with 4'-deoxy-4'-iodo-doxorubicin (4'-I-Dx), a new Dx derivative. Dx was 200 times less active in resistant than in sensitive cells, whereas the iodo derivative compou...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262780
更新日期:1988-01-01 00:00:00
abstract::Dihydroartemisinin (DHA), a more water-soluble active metabolite of artemisinin derivatives, is safe and the most effective antimalarial analog of artemisinin. In the present investigation, we assessed the effect of DHA on vascular endothelial growth factor (VEGF) expression and apoptosis in chronic myeloid leukemia (...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0002-y
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to investigate typical population pharmacokinetic (PK) parameters, potential covariates, and interindividual and residual variabilities of PI-88, a heparanase endoglycosidase enzyme inhibitor being developed for the treatment of cancer. METHODS:A population PK model of PI-88 was devel...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1080-z
更新日期:2010-03-01 00:00:00
abstract::Studies are described in which a new folate analogue, edatrexate (EDX), in combination with the vinca alkaloids, vinblastine (VBL), navelbine (NVB) or vindesine (DVA) was evaluated against E0771 mammary adenocarcinoma, T241 fibrosarcoma and the Lewis lung tumor. Each of the four agents when given individually to anima...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685901
更新日期:1994-01-01 00:00:00
abstract::Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28 polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians. Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI-in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-017-3306-9
更新日期:2017-06-01 00:00:00
abstract:PURPOSE:Gastric cancer is one of the leading cancerous diseases worldwide. It is diagnosed often at the advanced stage for which chemotherapy is the main treatment option. The prognosis remains poor for metastatic, especially the diffuse type, gastric cancers. We investigated the efficacy of intravenously administered ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1222-3
更新日期:2010-09-01 00:00:00
abstract::Despite its rapid enzymatic inactivation and therefore limited activity in vivo, Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the drug, and achieve passive tumor targeting, we developed a liposomal formulation of Gemcitabine, GemLip (Ø: 36 nm: 47% entrapment). Its anti-tumoral activity ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0482-z
更新日期:2008-03-01 00:00:00
abstract::Seventy-three patients with Dukes' B2 and C colorectal cancer were randomized to adjuvant therapy after radical surgery. One group was treated with chemotherapy either alone or in combination with radiotherapy (RC). The second group was treated by chemotherapy (with or without radiotherapy) plus MER/BCG (RCM). In pati...
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/BF00292869
更新日期:1982-01-01 00:00:00
abstract::The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the poten...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-018-3541-8
更新日期:2018-05-01 00:00:00
abstract:INTRODUCTION:Limited information on second-line treatment in patients with pancreatic adenocarcinoma is available. At time of first-line treatment failure, approximately half of the patients are candidates for further treatment. MATERIAL AND METHODS:A retrospective review of 183 patients submitted to second-line thera...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-007-0653-y
更新日期:2008-09-01 00:00:00
abstract:PURPOSE:Efforts are underway in improving the informed consent process. The success of these efforts to improve quality of informed consent forms (ICFs) for phase I oncology trials has not been previously measured. METHODS:We reviewed and compared ICFs of all phase I trials for metastatic cancer conducted between 1986...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3673-x
更新日期:2018-11-01 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::In early studies of the antitumor drug 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1nitrosourea (methyl-CCNU), animal models consistently predicted that the compound would be nephrotoxic in humans. Nephrotoxicity in cancer patients who had received methyl-CCNU was not confirmed until about 6 years after clinical trials b...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257241
更新日期:1982-12-01 00:00:00
abstract:PURPOSE:Peritoneal dissemination is the most frequent and life-threatening mode of metastasis and recurrence in patients with gastric cancer. A multicenter phase II study was designed to evaluate the efficacy and tolerability of S-1 and docetaxel combination chemotherapy regimen for the treatment of advanced or recurre...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-013-2086-0
更新日期:2013-04-01 00:00:00
abstract::NQO1 is a reductive enzyme that is important for the activation of many bioreductive agents and is a target for an enzyme-directed approach to cancer therapy. It can be selectively induced in many tumor types by a number of compounds including dimethyl fumarate and sulforaphane. Mitomycin C is a bioreductive agent tha...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0961-4
更新日期:2005-09-01 00:00:00
abstract::Acute promyelocytic leukemia (APL) is characterized by the expansion of malignant myeloid cells blocked at the promyelocytic stage of hemopoietic development and is invariably associated with reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) gene on chromosome 17. RARalpha var...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s002800100322
更新日期:2001-08-01 00:00:00
abstract:PURPOSE:Although chemotherapeutic protocols that include chloroethylnitrosoureas (CENUs), such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), have been a mainstay of treatment for glioblastomas, the clinical outcomes ha...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050023
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:The aim of the present study was to develop a new strategy for combined thermo-chemotherapy of cancer. For this purpose, we used ultrasound waves [1 MHz; 1 W/cm2; 10 min] in combination with a sonosensitizing nanoplatform, named ACA, made of alginate co-loaded with cisplatin and gold nanoparticles (AuNPs). MET...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03961-9
更新日期:2019-12-01 00:00:00
abstract::Cyclophosphamide pharmacokinetics have been studied in 16 female patients with advanced breast cancer. The group included 7 patients who were greater than 20%, less than or equal to 30% over ideal body weight and 5 patients who were greater than 30% over ideal body weight. Cyclophosphamide plasma elimination half-live...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00570489
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:Fruquintinib (HMPL-013) is a novel, potent, and highly selective tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptors (1, 2 and 3). This study was conducted to investigate the metabolism, excretion, and pharmacokinetics of HMPL-013 after a single oral dose to healthy Chinese men....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3394-6
更新日期:2017-09-01 00:00:00
abstract:PURPOSE:To determine toxicities, maximally tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of MTA, a novel antifolate compound which inhibits the enzymes thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFT), and dihydrofolate reductase (DHFR). METHODS:Patients...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s002800050992
更新日期:1999-01-01 00:00:00
abstract::The radiosensitizing activity, acute toxicity, and pharmacokinetics of a new hypoxic cell radiosensitizer, potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802), were compared with those of misonidazole (MISO) and etanidazole (SR-2508). The radiosensitizing activity of KIH-802 was slightly higher than that of MISO a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897255
更新日期:1990-01-01 00:00:00