Abstract:
:The aim of this study was to evaluate the effect of coadministration of acid-reducing agents on the pharmacokinetic exposure of orally administered epidermal growth factor receptor inhibitor erlotinib, a drug that displays pH-dependent solubility. Two studies were conducted, the first with the proton pump inhibitor omeprazole and the second with the H2-receptor antagonist ranitidine. Twenty-four healthy male and female volunteers were enrolled in each study. Erlotinib was administered as a single oral 150 mg dose on day 1. After the washout a subsequent study period evaluated 150 mg erlotinib administered with the acid-reducing agent. Omeprazole (40 mg once daily) was given on days 11-14, concomitantly with erlotinib on day 15, and for two additional days (days 16-17). In the ranitidine study, on day 13, participants were randomized to either concomitant dosing (treatment B) or staggered administration (treatment C) of erlotinib and ranitidine and crossed over to the other treatment starting on day 27. For treatment B, ranitidine (300 mg once daily) was administered in the morning for 5 days, 2 h before erlotinib. For treatment C, ranitidine was administered as a divided dose (150 mg twice daily) for 5 days, with erlotinib given 10 h after the previous evening dose and 2 h before the next ranitidine morning dose. Plasma samples were obtained for determination of the concentrations of erlotinib and its metabolite OSI-420, following each erlotinib dose. All participants were monitored for safety and tolerability. The geometric mean ratios of AUC0-∞ and Cmax for erlotinib and AUC0-last and Cmax for OSI-420 were substantially decreased when erlotinib was dosed with omeprazole. The estimated mean ratio (90% confidence interval) for erlotinib was 0.54 (0.49-0.59) for AUC0-∞ and 0.39 (0.32-0.48) for Cmax. For OSI-420, the estimated mean ratio was 0.42 (0.37-0.48) for AUC0-last and 0.31 (0.24-0.41) for Cmax. AUC0-∞ and Cmax for erlotinib were substantially decreased by 33 and 54%, respectively, upon coadministration with ranitidine, but the decrease was only 15 and 17% when ranitidine and erlotinib were given staggered. Similar results were observed for the metabolite OSI-420. Erlotinib was generally well-tolerated alone or in combination with omeprazole or ranitidine. Erlotinib pharmacokinetic exposure was substantially reduced upon coadministration with omeprazole and ranitidine, but not when administered with a staggered dosing approach to ranitidine. Therefore, it is recommended that the concomitant use of erlotinib with proton pump inhibitors be avoided. If treatment with an H2-receptor antagonist such as ranitidine is required, erlotinib must be administered 10 h after the H2-receptor antagonist dosing and at least 2 h before the next dose of the H2-receptor antagonist.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Kletzl H,Giraudon M,Ducray PS,Abt M,Hamilton M,Lum BLdoi
10.1097/CAD.0000000000000212subject
Has Abstractpub_date
2015-06-01 00:00:00pages
565-72issue
5eissn
0959-4973issn
1473-5741journal_volume
26pub_type
杂志文章,随机对照试验abstract::Declopramide (3-chloroprocainamide) has been identified in previous studies as a representative of a new class of chemosensitizers. In this study, the toxicity and pharmacokinetics of declopramide have been investigated and compared with a structural analog, metoclopramide (MCA). Declopramide has not induced central n...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199901000-00010
更新日期:1999-01-01 00:00:00
abstract::The epithelial-mesenchymal transition (EMT) plays an important role in inducing cancer metastasis. Baicalin, a flavone derivative isolated from Scutellaria spp., shows a series of pharmacological and physiological activities. However, the possible role of baicalin in the EMT is unclear. In this study, we attempted to ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000495
更新日期:2017-07-01 00:00:00
abstract::Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is a colorectal cancer (CRC) stem cell marker. The role of Lgr5-expressing stem cells in resistance to chemotherapy is controversial. The notion that Lgr5-expressing cells are more chemotherapy resistant is supported by some data; other data do not sup...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000270
更新日期:2015-10-01 00:00:00
abstract::Previous investigations have indicated the possibility to circumvent multidrug resistance (MDR) by incorporation of an anthracycline into liposomes. We examined the in vitro cytotoxicity and cellular drug accumulation of the anthracyclines daunorubicin and doxorubicin compared with the commercially available liposomal...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199911000-00008
更新日期:1999-11-01 00:00:00
abstract::Lung cancer is considered the number one killer among all cancers. Recent observations have altered the treatment paradigm for non-small-cell lung cancer (NSCLC). The discovery of activating mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase positivity has made personalized treatment for ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3283585149
更新日期:2012-11-01 00:00:00
abstract::Cancer stem cells play a fundamental role in the growth, metastasis, recurrence, and chemoresistance of cancers of various origins; therefore, targeting these cells may prospectively help to eradicate cancer cells from patients. In this study, the effect of tetrandrine on the proliferation of CD133-positive (CD133) He...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000803
更新日期:2019-10-01 00:00:00
abstract::C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC wer...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000417
更新日期:2016-11-01 00:00:00
abstract::Response rates reported in early phase II clinical trials are often not reproduced in subsequent larger or phase III studies. Independent review of claimed partial or complete responders to gemcitabine was undertaken in four pivotal, open-label phase II studies of advanced, non-small cell lung cancer (NSCLC) to provid...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199909000-00001
更新日期:1999-09-01 00:00:00
abstract::Epidemiological and clinical studies suggesting a significant inverse relationship between intake of dietary selenium and overall cancer risk have led to initiation of a randomized, placebo-controlled, phase III clinical trial testing the safety and efficacy of selenized yeast as a chemopreventive agent for prostate c...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/00001813-200309000-00003
更新日期:2003-09-01 00:00:00
abstract::The use of viability assays to assess the effect of antineoplastic agents on cell lines and tumor cells is an important investigative tool and may have clinical relevance. Such assays require very small quantities of drugs and it is the practice of many laboratories to freeze aliquots of drugs for use in these assays ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199404000-00007
更新日期:1994-04-01 00:00:00
abstract::Glioma is a primary intracranial malignant tumor with poor prognosis. In this study, we aimed to develop transferrin (Tf)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles to deliver temozolomide (TMZ) to glioma and evaluate their efficacy to kill glioma. TMZ-loaded nanoparticles were prepared by nanoprecipi...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000754
更新日期:2019-07-01 00:00:00
abstract::Paclitaxel and docetaxel are excellent agents with a high antitumor effect for the treatment of previously anthracycline-exposed metastatic breast cancer. There has been no standard treatment for patients who undergo therapy of a taxan-resistant metastatic breast cancer. Paclitaxel has partial non-cross-resistance in ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200008000-00008
更新日期:2000-08-01 00:00:00
abstract::Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200606000-00007
更新日期:2006-06-01 00:00:00
abstract::Paeonol, a major phenolic component of Moutan Cortex, is known to have antitumor effects through an unknown mechanism. In this study, we tried to elucidate the anticancer effects of paeonol on human hepatocellular carcinoma (HCC) cell lines BEL-7404, SMMC-7721, and MHCC97-H in vitro. Using the 3-[4,5-dimethylthiazol-2...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3282f7f4eb
更新日期:2008-04-01 00:00:00
abstract::Long noncoding RNA (lncRNA) KTN1 antisense RNA 1 (KTN1-AS1) is a novel promoter in the progression of some cancers. However, the knowledge of its role in lung adenocarcinoma is still limited. The current study aimed to examine the biological functions of KTN1-AS1 and its coexpressed protein in lung adenocarcinoma. The...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000001035
更新日期:2021-01-22 00:00:00
abstract::Docetaxel is a new antimicrotubule agent that induces a predominantly sensory neuropathy that is mild in most patients. This prospective study was performed to determine if corticosteroid co-medication reduces the incidence and severity of docetaxel-induced neuropathy. Two groups of patients treated with docetaxel in ...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/00001813-199810000-00003
更新日期:1998-10-01 00:00:00
abstract::Temozolomide (TMZ) combination with whole-brain radiotherapy (WBRT) has been tested by many randomized controlled trials in the treatment of brain metastases (BMs) in China and other countries. We performed an up-to-date meta-analysis to determine (i) the log odds ratios (LORs) of objective response (ORR) and adverse ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,meta分析,评审
doi:10.1097/CAD.0000000000000295
更新日期:2016-01-01 00:00:00
abstract::Panitumumab has proven efficacy in patients with metastatic or locally advanced colorectal cancer patients, provided that they have no activating KRAS mutation in their tumour. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification of KRAS. We hypothesize that the act...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,多中心研究
doi:10.1097/CAD.0000000000000255
更新日期:2015-09-01 00:00:00
abstract::Aberrant expression of the epidermal growth factor receptor (EGFR) system has been reported in a wide range of epithelial cancers. In some studies, this has also been associated with a poor prognosis and resistance to the conventional forms of therapies. These discoveries have led to the strategic development of sever...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3283330590
更新日期:2009-11-01 00:00:00
abstract::We have established estrogen-independent and antiestrogen-resistant cell lines from hormone-dependent MCF-7 breast cancer cells by long-term culture in the absence of estrogen, or in the presence of antiestrogen toremifene, respectively. By using a cDNA microarray we compared gene expression profiles among estrogen-in...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32831845e1
更新日期:2009-01-01 00:00:00
abstract::There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by end...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283635a47
更新日期:2013-09-01 00:00:00
abstract::DNA has been one of the major targets of cancer chemotherapy. A variety of anti-neoplastic agents can cause different types of DNA lesions, including base alterations, single- or double-strand DNA breaks, DNA-DNA cross-links and DNA-protein cross-links. The exact processes by which these DNA lesions lead to cell death...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199112000-00003
更新日期:1991-12-01 00:00:00
abstract::We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32801265eb
更新日期:2007-04-01 00:00:00
abstract::(E)-2'-deoxy-2'-(fluoromethylene) cytidine (MDL101,731) is a new deoxycytidine analog which shows potent antitumor activity against several human tumor models. We previously showed that MDL101,731 inhibited human ribonucleotide reductase (RNR) in HeLa S3 human cervical carcinoma cells. Recently, it has been reported t...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199808000-00011
更新日期:1998-08-01 00:00:00
abstract::Glassy cell carcinoma (GCC) of the uterine cervix is a highly malignant tumor and has a poor prognosis. As yet, no effective systemic chemotherapy to this tumor has been reported. Here we describe a case of recurrent GCC that responded to paclitaxel and carboplatin combination treatment. The patient, a 32-year-old wom...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200108000-00010
更新日期:2001-08-01 00:00:00
abstract::Pancreatic neuroendocrine tumors (PNETs) are rare malignancies that arise from the islets of Langerhans. The role of standard chemotherapy in advanced well-differentiated PNETs remains to be defined. Sunitinib is an oral multitargeted inhibitor with antiangiogenic and antitumor properties that has shown significant im...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328344484b
更新日期:2011-06-01 00:00:00
abstract::Ecteinascidin 743 (Et743) is an interesting compound in phase II/III clinical trials. Its chemistry is complex, its mechanism of action is original and it is active in human cancers, such as sarcomas refractory to conventional chemotherapy. The present review describes the discovery of the drug, its specific interacti...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200207000-00001
更新日期:2002-07-01 00:00:00
abstract::In this study, we tried to define in vitro interactions of two antitumor agents that have different sites and different mechanisms of action. Vinblastine (VLB) in combination with human recombinant interferon-alpha A/D (rHuIFN-alpha A/D) and in combination with murine recombinant interferon-gamma (rMuIFN-gamma) was st...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199402000-00008
更新日期:1994-02-01 00:00:00
abstract::Metformin, an oral antidiabetic agent, has been reported to potentiate chemotherapeutic-induced cytotoxicity. In this study, we investigated the effects and molecular mechanisms of metformin in sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human bladder cancer cells. ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000116
更新日期:2014-09-01 00:00:00
abstract::The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth i...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835e5996
更新日期:2013-04-01 00:00:00