Abstract:
:Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. The lactone structure of topotecan, which is in equilibrium with the inactive ring-opened hydroxy acid, is essential for this activity. We performed a pharmacokinetics study as part of phase II clinical trials in patients with various types of solid tumors, giving topotecan at 1.5 mg/m2 per day by 30-min infusion for 5 consecutive days, with courses being repeated every 3 weeks. Previously validated limited-sampling models, using concentration measurements in samples obtained 2 h after infusion, were used to calculate the area under the plasma concentration-time curves (AUCs) for both chemical forms. Samples were obtained from a total of 36 patients over 136 treatment days. The mean AUC of the closed-ring form (AUC(closed)) was 8.74 (range 2.3-16.3 microM min per day, and the mean AUC of the ring-opened form (AUC(open)) was 11.5 (range 3.2-46.0) microM min per day (interpatient variability 34-61%). In each patient the AUC values achieved on the 1st day of administration were similar to and, thus, predictive for those achieved during the following days, with a day-to-day variation of 7.39% being recorded for the AUC(closed) and that of 12.6% for the AUC(open). There was no drug accumulation during the 5 consecutive treatment days of each cycle. However, despite the large interpatient pharmacokinetic variability, the importance of regular drug monitoring on this schedule can be questioned, as the pharmacodynamic variability was relatively small.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
van Warmerdam LJ,Creemers GJ,Rodenhuis S,Rosing H,de Boer-Dennert M,Schellens JH,ten Bokkel Huinink WW,Davies BE,Maes RA,Verweij J,Beijnen JHdoi
10.1007/s002800050479subject
Has Abstractpub_date
1996-01-01 00:00:00pages
254-60issue
3eissn
0344-5704issn
1432-0843journal_volume
38pub_type
临床试验,杂志文章abstract::The effect of 7-alkyl substitutions on growth inhibition in seven Camptothecin (CPT) ring systems with various groups at the ten position was evaluated in three human breast cancer cell lines that model (1) hormone-sensitive (MCF-7/wt), (2) hormone insensitive (MDA-MB-231), or (3) alkylator-resistant (MCF-7/4-hc) form...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0007-6
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:The ERCC1-XPF 5'-3' DNA endonuclease complex is involved in the nucleotide excision repair pathway and in the DNA inter-strand crosslink repair pathway, two key mechanisms modulating the activity of chemotherapeutic alkylating agents in cancer cells. Inhibitors of the interaction between ERCC1 and XPF can be us...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04213-x
更新日期:2021-01-05 00:00:00
abstract::Thirty-three patients with advanced transitional cell carcinoma of the urinary tract (23 bladder cases, 8 ureter cases, and 2 renal pelvis cases) were treated by three-drug combination chemotherapy using two protocols (protocol I: Adriamycin 50 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 500 mg/m2, protocol ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256716
更新日期:1983-01-01 00:00:00
abstract:PURPOSE:The purpose of these extensive non-clinical studies was to assess pharmacokinetics and dispositional properties of sunitinib and its primary active metabolite (SU12662). METHODS:Sunitinib was administered in single and repeat oral doses in mice, rats, and monkeys. Assessments were made using liquid-chromatogra...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0917-1
更新日期:2009-09-01 00:00:00
abstract:PURPOSE:The purpose of this study was to evaluate the safety and efficacy of low-dose-intensity bevacizumab and weekly irinotecan as salvage treatment for patients with platinum- and taxanes-resistant advanced epithelial ovarian cancer. METHODS:Fifty-two patients with platinum- and taxanes-resistant advanced epithelia...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2680-4
更新日期:2015-03-01 00:00:00
abstract::Larotaxel (XRP9881, RPR109881), a novel semi-synthetic taxoid that shares a mode of action with the taxanes docetaxel and paclitaxel, was active in preclinical studies against a broad spectrum of tumour cells and tumour models refractory/resistant to taxanes, and have demonstrated clinical activity in taxane pre-treat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1014-9
更新日期:2009-12-01 00:00:00
abstract:PURPOSE:This study was performed to determine the maximum tolerated dose (MTD) and toxicity of vinorelbine when used in combination with doxorubicin and methotrexate with leucovorin rescue in women with metastatic breast cancer. METHODS:Enrolled in the study were 23 women with metastatic breast cancer who had not rece...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050929
更新日期:1999-01-01 00:00:00
abstract::In this review of the management of invasive carcinoma of the bladder the results of primary and systemic therapies are evaluated in the light of the natural history of the disease. The clinical and pathological causes of treatment failure are assessed in an attempt to identify new approaches that may be used in the f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00254978
更新日期:1979-01-01 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:Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-018-3567-y
更新日期:2018-05-01 00:00:00
abstract::The toxicity of single doses of the anthracycline epirubicin was compared in the rat after either the intravenous (i.v.; 2-6 mg/kg) or intraperitoneal (i.p.; 4-8 mg/kg) administration of the drug. These doses produced comparable acute toxicity that was characterised by a dose-dependent, transient reduction in body wei...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257620
更新日期:1989-01-01 00:00:00
abstract::In order to determine if any inherent sensitivity differences may exist between VP16-213 and VM26 individual human tumors were grown in vitro and drug sensitivities were determined using the soft agar clonogenic assay method. Only nine of the 34 tumors tested so far showed a differing sensitivity to VP16-213 and VM26 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254531
更新日期:1982-01-01 00:00:00
abstract::Seventeen patients with malignant mesothelioma were treated in a phase II study with carboplatin, a cisplatin analogue without significant nephrotoxicity or neurotoxicity. The drug was given in a dose of 300-400 mg/m2 by i.v. infusion, repeating at 28-day intervals. One patient achieved a complete clinical and radiolo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00273404
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:We wished to define the maximum tolerated dose (MTD), toxicity, and pharmacokinetics of the novel isoflav-3-ene, NV06 (Phenoxodioltrade mark), a compound with a diphenolic structure related chemically and biologically to genistein and flavopiridol. PATIENTS AND METHODS:Twenty-one patients with advanced canc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0189-6
更新日期:2006-10-01 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:OBJECTIVE:To investigate the effects of FSTL1-mediated NF-κB signaling pathway on cisplatin (DDP) sensitivity of EOC cells. METHODS:FSTL1 expression was determined in epithelial ovarian cancer (EOC) tissues and corresponding adjacent tissues using immunohistochemistry. SKOV3 and SKOV3/DDP cells were transfected and gr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04215-9
更新日期:2021-01-03 00:00:00
abstract::Severe, debilitating nausea and vomiting are seen in almost 100% of patients treated with cis-platinum. These side-effects can be so severe and prolonged as to preclude therapy in a large number of patients. Commonly used antiemetics have had only limited success in controlling cis-platinum-induced nausea and vomiting...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258206
更新日期:1981-01-01 00:00:00
abstract::A series of in vitro cytotoxicity studies were performed to achieve pharmacologic reversal of resistance to the alkylating agent mitomycin (MMC) in L-1210 leukemia cells. A multidrug-resistant (MDR), P-glycoprotein-positive cell line, RL-1210/.1 [11], was exposed to potential MDR modulators in the absence or presence ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685114
更新日期:1991-01-01 00:00:00
abstract::The aim of the present investigation was to evaluate the potential cardioprotective effect of reduced glutathione (GSH) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a well-documented rat model. DXR was administered i.v. at a weekly dose of 3 mg/kg for a total of 4 doses; 250 or 500 mg/kg of GSH w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685691
更新日期:1991-01-01 00:00:00
abstract::A total of 26 evaluable patients with previously untreated, non-resectable adenocarcinoma of the lung were given 80 mg/m2 i.v. teniposide daily for 5 days every 3 weeks. Three partial responses (11%) were obtained that lasted for 12, 11 and 32 weeks, respectively. Leucopenia was the dose-limiting side effect, with WBC...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685166
更新日期:1991-01-01 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: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::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::A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435840
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The interindividual variability of vincristine pharmacokinetics is quite large, but the origins of this variability are not properly understood. The aim of this study was to develop a population pharmacokinetic model of vincristine in a paediatric population treated for solid tumour disease and evaluate the imp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1541-4
更新日期:2011-11-01 00:00:00
abstract:PURPOSE:To investigate the antitumor efficacy of pingyangmycin (PYM) in combination with anti-PD-1 antibody and determine the capability of PYM to induce immunogenic cell death (ICD) in cancer cells. METHODS:The murine 4T1 breast cancer and B16 melanoma models were used for evaluation of therapeutic efficacy of the co...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04209-7
更新日期:2021-01-03 00:00:00
abstract::The mechanisms of cytotoxicity, cellular drug uptake, intracellular drug distribution, cellular pharmacokinetics, formation of arabinofuranosylcytosine triphosphate (ara-CTP), and DNA incorporation of N4-hexadecyl-1-beta-D-arabinofuranosylcytosine (NHAC), a new lipophilic derivative of arabinofuranosylcytosine (ara-C)...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685798
更新日期:1995-01-01 00:00:00
abstract::The pharmacokinetics of soluble oral prednisolone were studied during induction therapy in six children with acute lymphoblastic leukaemia. There was a three- to four-fold variation in the pharmacokinetics of total and free prednisolone. For total prednisolone, the mean elimination half-life was relatively short (1.37...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435843
更新日期:1989-01-01 00:00:00
abstract::Etoposide is a widely used cytotoxic drug that requires complex formulation for both the i.v. and oral preparation to ensure drug stability. Data on the stability of the i.v. formulation when diluted in infusion fluids are contradictory, and there is little information on the stability of the oral preparation in gastr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685638
更新日期:1995-01-01 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