Abstract:
PURPOSE:The combination of an mTOR inhibitor with 5-fluorouracil-based anticancer therapy is attractive because of preclinical evidence of synergy between these drugs. According to our phase I study, the combination of capecitabine and everolimus is safe and feasible, with potential activity in pancreatic cancer patients. METHODS:Patients with advanced adenocarcinoma of the pancreas were enrolled. Eligible patients had a WHO performance status 0-2 and adequate hepatic and renal functions. The treatment regimen consisted of capecitabine 1000 mg/m(2) BID day 1-14 and everolimus 10 mg daily (5 mg BID) in a continuous 21-day schedule. Tumor assessment was performed with CT-scan every three cycles. Primary endpoint was response rate (RR) according to RECIST 1.0. Secondary endpoints were progression-free survival, overall survival and 1-year survival rate. RESULTS:In total, 31 patients were enrolled. Median (range) treatment duration with everolimus was 76 days (1-431). Principal grade 3/4 toxicities were hyperglycemia (45 %), hand-foot syndrome (16 %), diarrhea (6 %) and mucositis (3 %). Prominent grade 1/2 toxicities were anemia (81 %), rash (65 %), mucositis (58 %) and fatigue (55 %). RR was 6 %. Ten patients (32 %) had stable disease resulting in a disease control rate of 38 %. Median overall survival was 8.9 months (95 % CI 4.6-13.1). Progression-free survival was 3.6 months (95 % CI 1.9-5.3). CONCLUSIONS:The oral regimen with the combination of capecitabine and everolimus is a moderately active treatment for patients with advanced pancreatic cancer, with an acceptable toxicity profile at the applied dose level.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Kordes S,Klümpen HJ,Weterman MJ,Schellens JH,Richel DJ,Wilmink JWdoi
10.1007/s00280-015-2730-ysubject
Has Abstractpub_date
2015-06-01 00:00:00pages
1135-41issue
6eissn
0344-5704issn
1432-0843journal_volume
75pub_type
杂志文章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::Ever since the estrogen receptor (ER) beta was discovered in 1996, we have been trying to determine its value as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. Recent progress in cellular experiments has shown that ERbeta works as counter pa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-005-0107-3
更新日期:2005-11-01 00:00:00
abstract::Saturable elimination of 5-FU is exhibited in rats during constant infusions. Over the range of 3-480 mg/m2/h, total-body clearance of 5-FU decreases from 600 ml/min/m2 to less than 90 ml/min/m2. Previously published values for catabolism of 5-FU by rat hepatocytes can be used to simulate the plasma concentrations of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434346
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:Evasion to new treatments of advanced melanoma is still associated with a poor prognosis. Choosing the best combination of agents that can bypass resistance mechanisms remains a challenge. Sphaeropsidin A (Sph A) is a fungal bioactive secondary metabolite previously shown to force melanoma cells to undergo apop...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3293-x
更新日期:2017-05-01 00:00:00
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...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1850-x
更新日期:2012-06-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs. METHODS:The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from pa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1746-1
更新日期:2012-03-01 00:00:00
abstract::GR63178A is the second pentacyclic pyrroloquinone to enter clinical trials as an anticancer drug. We developed a reversed-phase, gradient-elution high-performance liquid chromatography (HPLC) method along with a Bond Elut C2 mini-column sample-preparation technique for the analysis of GR63178A, its 9-hydroxy-metabolit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00684952
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Temozolomide (TMZ) is a widely used oral alkylating agent that has been associated with the development of severe hematologic adverse events (HAEs). Limited clinical information about HAEs is available. METHODS:We searched the FDA MedWatch database for TMZ and obtained all MedWatch reports on TMZ submitted to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1679-8
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:Trametinib is a reversible, selective inhibitor of the mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and 2 (MEK2). Cardiotoxicity (congestive heart failure, decreased heart rate, left ventricular dysfunction, and hypertension) related to trametinib is an infrequent, but serious, adverse event...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-016-3090-y
更新日期:2016-09-01 00:00:00
abstract::2'-deoxycoformycin (2'-dCF; Pentostatin), a stoichiometric inhibitor of mammalian adenosine deaminase (ado deaminase), exhibits immunosuppressive and antilymphocytic activity in animal test systems. A clinical pharmacology/phase I study of 2'-dCF administered as a single agent has been completed (18 patients). Dose le...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435411
更新日期:1980-01-01 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: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::Macroautophagy is widely accepted as a cytoprotective mechanism against various environmental stresses. While inhibition of autophagy is generally considered to increase the susceptibility of cancer cells to therapeutic agents, whether it also plays a similar role in tumor stem cells is unclear and still controversial...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-014-2634-2
更新日期:2015-05-01 00:00:00
abstract::1-Hexylcarbamoyl-5-fluorouracil (HCFU) and its parent compound 5-fluorouracil (5-FU) were tested PO for antitumor activity against mouse colon adenocarcinoma 26 (colon 26), colon adenocarcinoma 38 (colon 38), and Lewis lung carcinoma. The drugs were given orally at 2--4 days intervals for a total of ten doses. 5-FU wa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254027
更新日期:1980-01-01 00:00:00
abstract::Bizelesin (U-77779) is a highly potent bis-alkylating antitumor agent that is effective against several tumor systems in vitro and in vivo. V79 cells that were 125- to 250-fold resistant to bizelesin developed after constant exposure to gradually increasing concentrations of the drug. Resistant cells exhibited a multi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686110
更新日期:1994-01-01 00:00:00
abstract::The consequences at the cardiac level of adriamycin treatment alone or in association with the cardiac glycoside beta-methyldigoxin, were evaluated with reference to the PEP/LVET ratio, heart rate, and minimum blood pressure. The variation usually seen in the PEP/LVET ratio when adriamycin is administered alone was no...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258290
更新日期:1979-01-01 00:00:00
abstract:PURPOSE:In this study the maximum tolerated dose of 5-fluorouracil administered by 5-day (120-h) continuous infusion every 4 weeks was investigated and the pharmacokinetics in patients with hepatocellular carcinoma were evaluated. METHODS:Patients with hepatocellular carcinoma no longer amenable to established forms o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-001-0400-8
更新日期:2002-02-01 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::The antitumor effects of human lymphoblastoid interferon (HLBI) on human renal cell carcinomas transplanted in nude mice, i.e., KU-2 and RCC-1, were investigated and compared with those on other human tumors, viz. HeLa (cervical carcinoma), KB (nasopharyngeal carcinoma), H.Ep#2 (laryngeal carcinoma), and MX-1 (breast ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258113
更新日期:1985-01-01 00:00:00
abstract::Melphalan (L-PAM) pharmacokinetics were investigated in nine ovarian cancer patients before and after cisplatin (DDP) treatment. When L-PAM was given 24 h before DDP, the elimination half-life (t 1/2 beta), plasma clearance (Clp), and volume of distribution (Vd beta) of L-PAM were, respectively: 46.4 +/- 6.7 min, 20.5...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254189
更新日期:1988-01-01 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:PURPOSE:Pegylated liposomal doxorubicin (PLD) is used to treat patients with breast and gynecological cancers. In order to optimize treatment with PLD, we assessed the prognostic and predictive factors for efficacy of PLD. METHODS:Seventeen patients treated with PLD 30 or 40 mg/m(2) underwent pharmacokinetic sampling ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2514-9
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:There are no clear predictors clinicians can use to determine who is more likely to experience dose-limiting toxicity (DLT) in phase I chemotherapy clinical trials. Many providers are reluctant to refer older adults to phase I trials because of concerns about the development of toxicity. The goal of this stu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1084-8
更新日期:2010-03-01 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: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::Thirty-five patients with a diagnosis of non-Hodgkin's lymphoma of low histological grade were treated with 2 X 10(6)/m2 of human rDNA alpha 2 IFN-a2 by subcutaneous injection. Treatment was continued until progressive disease was documented or one year of therapy had been given. None of the patients had to stop treat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00253065
更新日期:1986-01-01 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:PURPOSE:The blood-brain barrier discriminates the access of several molecules to the brain. This hampers the use of some drugs, as doxorubicin, potentially active for treatment of brain tumors. We explored the feasibility of active modification of the blood-brain barrier protection, by using morphine pretreatment, to a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1429-3
更新日期:2011-06-01 00:00:00
abstract:PURPOSE:One of the major problems of cancer chemotherapy is the development of multidrug resistance (MDR) phenotype. Among the numerous mechanisms of MDR, a prominent one is the increased expression of membrane transporter proteins, the action of which leads to decreased intracellular drug concentration and cytotoxicit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1385-y
更新日期:2011-04-01 00:00:00
abstract::The metabolic disposition and pharmacokinetics of TNP-470 were investigated in rhesus monkeys following intravenous administration of 5 mg/kg of [3H]-TNP-470. Rapid and extensive metabolism of parent drug to six metabolites occurred as demonstrated by the absence of unchanged drug in plasma and urine at time points as...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050458
更新日期:1996-01-01 00:00:00