Abstract:
:Gefitinib (an epidermal growth factor receptor tyrosine kinase inhibitor) and bexarotene (a rexinoid) affect similar oncogenic pathways and are both metabolized through cytochrome P450 CYP3A4. We studied the combination of bexarotene and gefitinib in the third-line treatment of advanced non-small-cell lung cancer to examine pharmacokinetic interactions and establish the maximum tolerated dose. This was a single-institution, nonrandomized, open-label, phase I clinical trial with a standard 3+3 dose escalation. Three patients were enrolled at each dose level on the basis of pharmacokinetic analysis with dose level 1 including gefitinib (Iressa) 250 mg oral daily and bexarotene (Targretin) 400 mg/m oral daily and dose level +1 including gefitinib 500 mg oral daily and bexarotene 400 mg/m oral daily. Patients received gefitinib alone for 2 weeks to allow for steady state and thereafter, bexarotene was added. In dose level 1, two of three patients had undetectable gefitinib levels at day 15 for unknown reasons. However, the peak levels on day 29 for all three patients receiving 250 mg of gefitinib with bexarotene are lower than published peak levels. Among the three patients in dose level +1, ∼40% lower gefitinib plasma concentrations were noted on day 29 compared with day 15 along with a mean 44% reduction in area under the plasma concentration-time curve from 0 to 24 h (AUC0-24). Bexarotene appears to lower the C max and AUC0-24 of gefitinib through cytochrome P450 CYP3A4. Our results have pharmacokinetic implications for ongoing trials that combine bexarotene with other small molecules in the era of personalized cancer therapy.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Padda SK,Chhatwani L,Zhou L,Jacobs CD,Lopez-Anaya A,Wakelee HAdoi
10.1097/CAD.0b013e32836100d7subject
Has Abstractpub_date
2013-08-01 00:00:00pages
731-5issue
7eissn
0959-4973issn
1473-5741journal_volume
24pub_type
杂志文章abstract::E7070 is a novel sulfonamide anticancer agent that arrests the G(1)/S phase of the cell cycle. Preclinical and phase I studies have demonstrated non-linear pharmacokinetics (PK) of the drug. A population PK analysis revealed that the human plasma concentration-time data were best described by a three-compartment model...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200307000-00003
更新日期:2003-07-01 00:00:00
abstract::The aim of this review is to summarize currently available information on the rapid screening and initial characterization of the different mechanisms of resistance to hydrophilic [e.g. methotrexate (MTX)] and lipophilic antifolates [e.g. trimetrexate (TMTX)] in cultured mammalian cells using fluorescein-methotrexate ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199310000-00002
更新日期:1993-10-01 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::Since 5-fluorouracil (5-FU) was synthesized in the late 1950s it has become an important component of many anticancer treatment regimens. The increasing volume of literature accumulating about this drug is evidence that the optimal administration schedule and its combination with modulators has yet to be determined. M...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199406000-00002
更新日期:1994-06-01 00:00:00
abstract::In a retrospective study, we calculated the treatment and follow-up costs of patients with newly diagnosed multiple myeloma. The total treatment programme consisted of eight phases: VAD or VAMP chemotherapy, follow-up I, high-dose melphalan followed by transplantation of whole blood, follow-up II, collection of periph...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199811000-00008
更新日期:1998-11-01 00:00:00
abstract::This trial aimed to define a recommended safe dose (RSD) of weekly paclitaxel and irinotecan combined with carboplatin in patients with advanced cancer. Patients with advanced cancer were eligible for this trial. Dose-limiting toxicity (DLT) was considered to be any grade greater than or equal to 3 (G> or =3) nonhemat...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32833d5ec0
更新日期:2010-09-01 00:00:00
abstract::Multi-targeted antifolate (MTA) is an anti-metabolite with useful activity in the treatment of non-operable patients presenting with non-small cell lung cancer. Its good efficacy and tolerability profile as first-line therapy was demonstrated in phase II studies of MTA as monotherapy. The use of MTA as second-line the...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:
更新日期:2001-07-01 00:00:00
abstract::Norcantharidin (NCTD), a chemically modified form of cantharidin, is a potential anticancer drug. This study investigated the effect of NCTD on anoikis in CT26 colorectal adenocarcinoma cells. NCTD treatment of CT26 cells showed a dose-dependent and time-dependent decrease in viability and cell proliferation. Growth i...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3282f18826
更新日期:2008-01-01 00:00:00
abstract::In recent years, many diseases including cancer and hereditary and viral diseases have been understood at the DNA sequence level. Direct control of the expression level of a specific gene would provide a promising approach for knowledge-based therapy. N-methylpyrrole and N-methylimidazole polyamides are a new type of ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e328334d8f9
更新日期:2010-03-01 00:00:00
abstract::Topoisomerase IIα is a nuclear enzyme that alters DNA topology. It is a well-known anticancer target and related to cell differentiation status. All-trans retinoic acid (ATRA), an important active metabolite of vitamin A, is a promising anticancer agent in numerous malignancies. However, there are little data on the e...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000241
更新日期:2015-08-01 00:00:00
abstract::The plasma pharmacokinetics of a second generation anthracycline derivative, idarubicin (Ida), have been studied in 17 patients with acute myelocytic leukemia (AML) and high risk features. The drug (10 mg/m2) was given in a randomized cross-over design as 3 min and 2 h infusions for three consecutive days. Cytosine ar...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00001813-199701000-00005
更新日期:1997-01-01 00:00:00
abstract::Cyclosporin A (CsA) is a calcium antagonist and can enhance the efficacy of some protein drugs, but its mechanism remains unknown. In this study, MAP30, a ribosome-inactivating protein reported to have apoptotic effects on cancer cells, was fused with S3, an epidermal growth factor receptor (EGFR)-targeting peptide. I...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000649
更新日期:2018-09-01 00:00:00
abstract::Interleukin-12 (IL-12) has important immunomodulatory effects on T and natural killer (NK) cells that might be exploited in anticancer treatment. Murine IL-12 models have shown antimetastatic and antitumor effects against murine tumors in vivo. Data on the effects of human IL-12 on human tumors are confined to 51Cr-re...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199605000-00006
更新日期:1996-05-01 00:00:00
abstract::Bifunctional chloroethylating cytostatic agents produce lethal DNA lesions, as a result of the formation of O6-alkylguanines. These lesions can be repaired by O6-methylguanine-DNA methyltransferase (MGMT). This ubiquitous nuclear and cytosolic enzyme removes the alkyl group by accepting it to the cysteine residue of i...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199608000-00012
更新日期:1996-08-01 00:00:00
abstract::Antibody-cytokine fusion proteins (also called 'immunocytokines') represent an emerging class of biopharmaceutical products, which are being considered for cancer immunotherapy. When used as single agents, pro-inflammatory immunocytokines are rarely capable of inducing complete and durable cancer regression in mouse m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000938
更新日期:2020-09-01 00:00:00
abstract::5-Fluorouracil, usually in combination with folinic acid, is widely used in the treatment of both colorectal and head and neck squamous cell cancer patients. Since 5-fluorouracil plus folinic acid and the antifolate thymidylate synthase inhibitor; raltitrexed have distinct mechanisms of action and toxicity profiles, w...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32809ef9b7
更新日期:2007-08-01 00:00:00
abstract::Trifluorothymidine (TFT) is a fluorinated thymidine analog that after conversion to its monophosphate derivative can inhibit thymidylate synthase (TS) and be incorporated into DNA. TFT is a good substrate for thymidine phosphorylase (TP), and the combination of TFT and a TP inhibitor (TPI), called TAS-102, has been de...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200503000-00007
更新日期:2005-03-01 00:00:00
abstract::We demonstrate that neurokinin A (NKA) and substance P (SP) play a role in the proliferation of the estrogen receptor-negative (ER-) cell line MDA-MB-231, a human breast carcinoma expressing both NK-1 and NK-2 receptors. In vitro experiments showed that the specific receptor antagonists MEN 11,467 (NK-1) and nepadutan...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200511000-00007
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abstract::Mitoxantrone is a DNA topoisomerase II poison commonly used for the treatment of hormone-refractory prostate cancer. The risk of secondary leukaemia is well described after mitoxantrone treatment in breast cancer and multiple sclerosis. Recent improvements of systemic chemotherapy increased the median survival in pati...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3280113324
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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
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
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abstract::Hormonal agents have a confirmed role in the management of postmenopausal women with receptor-positive advanced breast cancer. Until recently, tamoxifen has been the accepted agent for treating these patients. However, accumulating evidence suggests that the new antiaromatase agents will replace the antiestrogens as t...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200304000-00003
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abstract::Concurrent and pre-exposure of A431 human epidermoid cancer cells to UCN-01, an investigational anticancer drug, with 5-fluoro--2'-deoxyuridine (FdUrd), which targets thymidylate synthase, produced more than additive cytotoxicty. A 24-h exposure to 10 nM FdUrd led to inhibition of TS, a 2.5-fold increase in total thym...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200203000-00008
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abstract::Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were de...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000934
更新日期:2020-08-01 00:00:00
abstract::In the past decade, tumour flare reaction (TFR) was considered as a new side effect associated with immunomodulatory agents (IMiDs) and as a condition of chronic lymphocytic leukaemia (CLL). However, this phenomenon is also observed with immune checkpoint inhibitors in solid tumours. It is still poorly understood and ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000814
更新日期:2019-10-01 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::RNA interference, a posttranscriptional gene-silencing mechanism, has received considerable attention for its potential as a new therapeutic strategy to treat human diseases and conditions including cancer. Various studies have supported a role for the R2 subunit of ribonucleotide reductase in cancer progression and m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328013c04f
更新日期:2007-04-01 00:00:00
abstract::Human colon cancer SW480 cells express the c-myc gene. On the other hand, SW480DDP cell lines resistant to cisplatin exhibited decreased c-myc gene expression, but their cell growth rates remained similar to those of their parental cells. Antisense oligonucleotides to c-myc inhibited c-myc expression and induced incre...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200111000-00006
更新日期:2001-11-01 00:00:00
abstract::The effects of 1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol (EDL-155) on the growth of glioma was tested in vitro and in vivo. Normal cultured rat astrocytes and C6 rat glioma were used as a differential screen to test the effects of EDL-155. The compound was preferentially cytotoxic for C6 glioma (...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32830d5887
更新日期:2008-10-01 00:00:00
abstract::This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studie...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:1992-06-01 00:00:00