Phase I and pharmacokinetic study of bexarotene in combination with gefitinib in the third-line treatment of non-small-cell lung cancer: brief report.

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 Drugs

journal_title

Anti-cancer drugs

authors

Padda SK,Chhatwani L,Zhou L,Jacobs CD,Lopez-Anaya A,Wakelee HA

doi

10.1097/CAD.0b013e32836100d7

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

731-5

issue

7

eissn

0959-4973

issn

1473-5741

journal_volume

24

pub_type

杂志文章
  • In vitro pharmacokinetic study of the novel anticancer agent E7070: red blood cell and plasma protein binding in human blood.

    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

    authors: Bongard HJ,Pluim D,Waardenburg RC,Ravic M,Beijnen JH,Schellens JH

    更新日期:2003-07-01 00:00:00

  • Characterization by flow cytometry and fluorescein-methotrexate labeling of hydrophilic and lipophilic antifolate resistance in cultured mammalian cells.

    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

    authors: Assaraf YG

    更新日期:1993-10-01 00:00:00

  • Gene expression changes during the development of estrogen-independent and antiestrogen-resistant growth in breast cancer cell culture models.

    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

    authors: Pennanen PT,Sarvilinna NS,Ylikomi TJ

    更新日期:2009-01-01 00:00:00

  • In vivo monitoring of fluoropyrimidine metabolites: magnetic resonance spectroscopy in the evaluation of 5-fluorouracil.

    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

    authors: Findlay MP,Leach MO

    更新日期:1994-06-01 00:00:00

  • Costs of intensive treatment and follow-up of patients with multiple myeloma.

    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

    authors: Buijt I,Ossenkoppele GJ,Uyl-de Groot CA,Huijgens PC

    更新日期:1998-11-01 00:00:00

  • Phase I trial of weekly irinotecan and paclitaxel combined with carboplatin in patients with advanced cancer: a Hellenic Cooperative Oncology Group Study.

    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

    authors: Briasoulis E,Golfinopoulos V,Karina M,Papakostas P,Pavlidis N,Fountzilas G

    更新日期:2010-09-01 00:00:00

  • [Multi-targeted antifolate therapy roe non-small cell lung cancer and mesothelioma].

    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:

    authors: Le Chevallier T

    更新日期:2001-07-01 00:00:00

  • Norcantharidin induces anoikis through Jun-N-terminal kinase activation in CT26 colorectal cancer cells.

    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

    authors: Chen YJ,Kuo CD,Tsai YM,Yu CC,Wang GS,Liao HF

    更新日期:2008-01-01 00:00:00

  • Anticancer activities of alkylating pyrrole-imidazole polyamides with specific sequence recognition.

    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

    authors: Shinohara K,Bando T,Sugiyama H

    更新日期:2010-03-01 00:00:00

  • All-trans retinoic acid suppresses topoisomerase IIα through the proteasomal pathway.

    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

    authors: Li X,Li Y,Shen X,Fu S,Han S,Feng Q

    更新日期:2015-08-01 00:00:00

  • Plasma pharmacokinetics of idarubicin and its 13-dihydro metabolite--a comparison of bolus versus 2 h infusion during a 3 day course.

    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

    authors: Eksborg S,Björkholm M,Hast R,Fagerlund E

    更新日期:1997-01-01 00:00:00

  • Enhanced anticancer effect of MAP30-S3 by cyclosproin A through endosomal escape.

    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

    authors: Song ZT,Zhang LW,Fan LQ,Kong JW,Mao JH,Zhao J,Wang FJ

    更新日期:2018-09-01 00:00:00

  • Antiproliferative effects of interleukin-12 treatment on human tumor colony-forming units taken directly from patients.

    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

    authors: Izquierdo MA,Degen D,Sypek JP,Von Hoff DD

    更新日期:1996-05-01 00:00:00

  • Circadian variation in O6-methylguanine-DNA methyltransferase activity in mouse liver.

    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

    authors: Martineau-Pivoteau N,Cussac-Buchdahl C,Chollet P,Rolhion C,Debiton E,Rapp M,Kwiatkowski F,Madelmont JC,Levi F

    更新日期:1996-08-01 00:00:00

  • The immunocytokine L19-TNF eradicates sarcomas in combination with chemotherapy agents or with immune check-point inhibitors.

    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

    authors: Corbellari R,Nadal L,Villa A,Neri D,De Luca R

    更新日期:2020-09-01 00:00:00

  • Synergistic antitumour effect of raltitrexed and 5-fluorouracil plus folinic acid combination in human cancer cells.

    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

    authors: Avallone A,Di Gennaro E,Bruzzese F,Laus G,Delrio P,Caraglia M,Pepe S,Comella P,Budillon A

    更新日期:2007-08-01 00:00:00

  • Determinants of trifluorothymidine sensitivity and metabolism in colon and lung cancer cells.

    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

    authors: Temmink OH,de Bruin M,Comijn EM,Fukushima M,Peters GJ

    更新日期:2005-03-01 00:00:00

  • Role of NK-1 and NK-2 tachykinin receptor antagonism on the growth of human breast carcinoma cell line MDA-MB-231.

    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

    authors: Bigioni M,Benzo A,Irrissuto C,Maggi CA,Goso C

    更新日期:2005-11-01 00:00:00

  • Mitoxantrone-related acute myeloblastic leukaemia in a patient with metastatic hormone-refractory prostate cancer.

    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

    authors: Martinez V,Mir O,Dômont J,Bouscary D,Goldwasser F

    更新日期:2007-02-01 00:00:00

  • Long noncoding RNA KTN1 antisense RNA 1exerts an oncogenic function in lung adenocarcinoma by regulating DEP domain containing 1 expression via activating epithelial-mesenchymal transition.

    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

    authors: Li YY,Li W,Chang GZ,Li YM

    更新日期:2021-01-22 00:00:00

  • Exploring the lack of cross-resistance between aromatase inhibitors: evidence for a difference?

    abstract::A lack of cross-resistance between the aromatase inhibitors (AIs) provides evidence to suggest that there are clinical differences between these agents. Available data from clinical trials indicate that patients exposed to nonsteroidal AIs may benefit from a steroidal compound of similar biochemical potency, and durab...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/01.cad.0000277875.81122.25

    authors: Lønning PE

    更新日期:2008-03-01 00:00:00

  • Update on the current use of hormonals as therapy in advanced breast cancer.

    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

    authors: Vogel CL

    更新日期:2003-04-01 00:00:00

  • Biochemical and molecular effects of UCN-01 in combination with 5-fluorodeoxyuridine in A431 human epidermoid cancer cells.

    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

    authors: Grem JL,Danenberg KD,Kao V,Danenberg PV,Nguyen D

    更新日期:2002-03-01 00:00:00

  • Dexmedetomidine suppresses the progression of esophageal cancer via miR-143-3p/epidermal growth factor receptor pathway substrate 8 axis.

    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

    authors: Zhang P,He H,Bai Y,Liu W,Huang L

    更新日期:2020-08-01 00:00:00

  • Tumour flare reaction in cancer treatments: a comprehensive literature review.

    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

    authors: Taleb B A

    更新日期:2019-10-01 00:00:00

  • SW480 colorectal cancer cells that naturally express Lgr5 are more sensitive to the most common chemotherapeutic agents than Lgr5-negative SW480 cells.

    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

    authors: Planutis AK,Holcombe RF,Planoutene MV,Planoutis KS

    更新日期:2015-10-01 00:00:00

  • RNA interference targeting the R2 subunit of ribonucleotide reductase inhibits growth of tumor cells in vitro and in vivo.

    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

    authors: Avolio TM,Lee Y,Feng N,Xiong K,Jin H,Wang M,Vassilakos A,Wright J,Young A

    更新日期:2007-04-01 00:00:00

  • Modification of the sensitivity to cisplatin with c-myc over-expression or down-regulation in colon cancer cells.

    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

    authors: Funato T,Kozawa K,Kaku M,Sasaki T

    更新日期:2001-11-01 00:00:00

  • Effects, in an in-vivo model system, of 1,2,3,4-tetrahydroisoquinoline on glioma.

    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

    authors: Kang GS,Wang XD,Mohler ML,Kirichenko OV,Patil R,Orr WE,Miller DD,Geisert EE

    更新日期:2008-10-01 00:00:00

  • High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers.

    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

    doi:10.1097/00001813-199206000-00002

    authors: Muggia FM,Brown TD,Goodman PJ,Macdonald JS,Hersh EM,Fleming TR,Leichman L

    更新日期:1992-06-01 00:00:00