Docetaxel metabolism is not altered by imatinib: findings from an early phase study in metastatic breast cancer.


:Docetaxel is primarily metabolized by CYP3A4 and susceptible to alterations in clearance by CYP3A4 inhibition and induction. Imatinib is a CYP3A4 inhibitor. A phase I study of docetaxel and imatinib in metastatic breast cancer (MBC) was conducted to test the hypothesis that imatinib decreased docetaxel clearance. Docetaxel was administered weekly × 3 with daily imatinib, repeated every 28 days; during cycle 1, imatinib was started on day 8. Docetaxel and imatinib pharmacokinetics, and hepatic CYP3A4 activity (erythromycin breath test) were evaluated during cycles 1 and 2. Toxicity and efficacy were assessed. Twelve patients were enrolled to three docetaxel/imatinib dose levels: 20 mg/m(2)/600 mg (DL1), 25 mg/m(2)/600 mg (DL2), and 25 mg/m(2)/400 mg (DL2a). Median number of prior chemotherapy regimens was 2 (range, 0-8). Toxicities were primarily observed at DL2; dose-limiting toxicities were Grade 3 transaminase elevations and diarrhea, and 5 patients had grade 2 nausea. Two patients had partial responses (7 months); two stable disease (2 and 4 months); five had progressive disease. Despite a 42% decrease in CYP3A4 activity after 3 weeks of imatinib co-administration, docetaxel clearance was unchanged. Mean ± standard deviation steady-state imatinib trough concentration (2.6 ± 1.2 μg/ml) was approximately 2.6-fold higher than previously observed in other cancer populations, and likely contributed to the poor tolerability of the combination in MBC. In conclusion, imatinib inhibited CYP3A4 but did not affect docetaxel clearance. Clinically, further investigation of this combination in MBC is not warranted due to excessive toxicities. However, these unexpected pharmacokinetic findings support further investigation of mechanisms underlying docetaxel elimination pathways.


Connolly RM,Rudek MA,Garrett-Mayer E,Jeter SC,Donehower MG,Wright LA,Zhao M,Fetting JH,Emens LA,Stearns V,Davidson NE,Baker SD,Wolff AC




Has Abstract


2011-05-01 00:00:00












  • Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma.

    abstract::The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP. The antiangiogen...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Teicher BA,Holden SA,Dupuis NP,Kakeji Y,Ikebe M,Emi Y,Goff D

    更新日期:1995-01-01 00:00:00

  • FOXP3-positive regulatory T lymphocytes and epithelial FOXP3 expression in synchronous normal, ductal carcinoma in situ, and invasive cancer of the breast.

    abstract::FOXP3-expressing T regulatory lymphocytes (Tregs) have been described as putative mediators of immune tolerance, and thus facilitators of tumor growth. When found in association with various malignancies, Tregs are generally markers of poor clinical outcome. However, it is unknown whether they are also associated with...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Lal A,Chan L,Devries S,Chin K,Scott GK,Benz CC,Chen YY,Waldman FM,Hwang ES

    更新日期:2013-06-01 00:00:00

  • Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study.

    abstract::Obesity and metabolic syndrome are risk and prognostic factors for breast cancer (BC) and are associated with chronic inflammation. We investigated the association between distinct BC subtypes and markers of adiposity, dysmetabolisms, and inflammation. We analyzed 1779 patients with primary invasive BC treated at a si...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Agresti R,Meneghini E,Baili P,Minicozzi P,Turco A,Cavallo I,Funaro F,Amash H,Berrino F,Tagliabue E,Sant M

    更新日期:2016-05-01 00:00:00

  • Distinct expressions of microRNAs that directly target estrogen receptor α in human breast cancer.

    abstract::Estrogen receptor (ER) α is essential for estrogen-dependent growth, and its level of expression is a crucial determinant of response to endocrine therapy and prognosis in ERα-positive breast cancer. Breast cancer patients show a wide range of ERα expression levels and the levels of expression in individual patients c...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Yoshimoto N,Toyama T,Takahashi S,Sugiura H,Endo Y,Iwasa M,Fujii Y,Yamashita H

    更新日期:2011-11-01 00:00:00

  • Tumor necrosis factor-alpha induces interleukin-6 production via extracellular-regulated kinase 1 activation in breast cancer cells.

    abstract::Interleukin-6 (IL-6) and interleukin-11 (IL-11) are frequently produced by breast cancer cells. These interleukins promote osteoclast formation and may mediate osteolysis at the site of breast cancer bone metastases. Transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Suarez-Cuervo C,Harris KW,Kallman L,Väänänen HK,Selander KS

    更新日期:2003-07-01 00:00:00

  • Shared decision-making in metastatic breast cancer: discrepancy between the expected prolongation of life and treatment efficacy between patients and physicians, and influencing factors.

    abstract::Treatment decisions in oncology are based on a balance between the efficacy of therapy and its side effects. Patients with metastases and patients with a limited prognosis are a particular challenge, since communication about the disease situation and the expected therapeutic benefit is difficult not only for patients...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Lux MP,Bayer CM,Loehberg CR,Fasching PA,Schrauder MG,Bani MR,Häberle L,Engel A,Heusinger K,Tänzer T,Radosavac D,Scharl A,Bauerfeind I,Gesslein J,Schulte H,Overbeck-Schulte B,Beckmann MW,Hein A

    更新日期:2013-06-01 00:00:00

  • Factors predicting the sentinel and non-sentinel lymph node metastases in breast cancer.

    abstract::The sentinel lymph node (SLN) is the only focus of axillary metastasis in a significant proportion of patients. In this single institutional study, clinicopathologic characteristics were investigated to determine the factors predicting the status of a SLN biopsy and the metastatic involvement of non-SLNs. Data were re...

    journal_title:Breast cancer research and treatment

    pub_type: 临床试验,杂志文章


    authors: Ozmen V,Karanlik H,Cabioglu N,Igci A,Kecer M,Asoglu O,Tuzlali S,Mudun A

    更新日期:2006-01-01 00:00:00

  • Estrogen switches pure mucinous breast cancer to invasive lobular carcinoma with mucinous features.

    abstract::Mucinous breast cancer (MBC) is mainly a disease of postmenopausal women. Pure MBC is rare and augurs a good prognosis. In contrast, MBC mixed with other histological subtypes of invasive disease loses the more favorable prognosis. Because of the relative rarity of pure MBC, little is known about its cell and tumor bi...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Jambal P,Badtke MM,Harrell JC,Borges VF,Post MD,Sollender GE,Spillman MA,Horwitz KB,Jacobsen BM

    更新日期:2013-01-01 00:00:00

  • Development of 95-gene classifier as a powerful predictor of recurrences in node-negative and ER-positive breast cancer patients.

    abstract::Our aim was to develop an accurate diagnostic system using gene expression analysis by means of DNA microarray for prognosis of node-negative and estrogen receptor (ER)-positive breast cancer patients in order to identify a subset of patients who can be safely spared adjuvant chemotherapy. A diagnostic system comprisi...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Naoi Y,Kishi K,Tanei T,Tsunashima R,Tominaga N,Baba Y,Kim SJ,Taguchi T,Tamaki Y,Noguchi S

    更新日期:2011-08-01 00:00:00

  • Breast-conserving surgery without axillary lymph node surgery or radiotherapy is safe for HER2-positive and triple negative breast cancer patients over 70 years of age.

    abstract:PURPOSE:The prognosis of elderly patients with hormone receptor-positive breast cancer is very good, and their survival is unaffected by performing breast-conserving surgery (BCS) without radiotherapy. Therefore, we aimed to verify that BCS without axillary lymph node dissection, sentinel lymph node biopsy, or radiothe...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Zhong Y,Xu Y,Zhou Y,Mao F,Lin Y,Guan J,Shen S,Pan B,Wang C,Peng L,Huang X,Li Y,Wang X,Sun Q

    更新日期:2020-07-01 00:00:00

  • Tumor marker phenotype concordance in second primary breast cancer, California, 1999-2004.

    abstract::Breast cancer is the most common cancer among women. It is estimated that 7% of women who have breast cancer will develop a subsequent second independent breast tumor within 10 years of the first. The status of estrogen (ER), progesterone (PR) and human growth hormone (HER2) receptors, individually and as phenotypic c...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Brown M,Bauer K,Pare M

    更新日期:2010-02-01 00:00:00

  • Inactivation of GPR30 reduces growth of triple-negative breast cancer cells: possible application in targeted therapy.

    abstract::Triple-negative breast cancers lack estrogen receptor α (ERα), progesterone receptor, and do not overexpress human epidermal growth factor receptor 2 (Her-2). They are neither susceptible to endocrine therapy nor to a therapy using the anti-Her-2 antibody, trastuzumab. Therefore, an efficient targeted therapy is warra...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Girgert R,Emons G,Gründker C

    更新日期:2012-07-01 00:00:00

  • Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women's Health Initiative observational study.

    abstract::Triple-negative breast cancer is a particularly aggressive and lethal breast cancer subtype that is more likely to be interval-detected rather than screen-detected. The purpose of this study is to discover and initially validate novel early detection biomarkers for triple-negative breast cancer using preclinical sampl...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Li CI,Mirus JE,Zhang Y,Ramirez AB,Ladd JJ,Prentice RL,McIntosh MW,Hanash SM,Lampe PD

    更新日期:2012-09-01 00:00:00

  • Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study.

    abstract::Metformin may exert anti-cancer effects through indirect (insulin-mediated) or direct (insulin-independent) mechanisms. We report results of a neoadjuvant "window of opportunity" study of metformin in women with operable breast cancer. Newly diagnosed, untreated, non-diabetic breast cancer patients received metformin ...

    journal_title:Breast cancer research and treatment

    pub_type: 临床试验,杂志文章


    authors: Niraula S,Dowling RJ,Ennis M,Chang MC,Done SJ,Hood N,Escallon J,Leong WL,McCready DR,Reedijk M,Stambolic V,Goodwin PJ

    更新日期:2012-10-01 00:00:00

  • Molecular detection of breast cancer metastasis in sentinel lymph nodes by reverse transcriptase polymerase chain reaction (RT-PCR): identifying, evaluating and establishing multi-marker panels.

    abstract::The potential advantage of using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) methodology to detect metastasis in sentinel lymph nodes (SLNs) of breast cancer (BC) patients was evaluated in this prospective study. We measured the expression of relevant gene transcripts in SLNs using an innova...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Wallwiener CW,Wallwiener M,Kurth RR,Röhm C,Neubauer H,Banys MJ,Staebler A,Schönfisch B,Meuer SC,Giese T,Fehm TN

    更新日期:2011-12-01 00:00:00

  • Pro-inflammatory cytokines and growth factors in human milk: an exploratory analysis of racial differences to inform breast cancer etiology.

    abstract:BACKGROUND:Analysis of cytokines and growth factors in human milk offers a noninvasive approach for studying the microenvironment of the postpartum breast, which may better reflect tissue levels than testing blood samples. Given that Black women have a higher incidence of early-onset breast cancers than White women, we...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Murphy J,Pfeiffer RM,Lynn BCD,Caballero AI,Browne EP,Punska EC,Yang HP,Falk RT,Anderton DL,Gierach GL,Arcaro KF,Sherman ME

    更新日期:2018-11-01 00:00:00

  • Early self-reported impairments in arm functioning of primary breast cancer patients predict late side effects of axillary lymph node dissection: results from a population-based cohort study.

    abstract:OBJECTIVES:Improvements in the life expectancy of women with breast cancer raise important questions how to improve quality of life (QoL) for women sustaining complications and side effects of cancer treatment. The presented study examined the prevalence of arm morbidity in a cohort of primary breast cancer patients ov...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Albert US,Koller M,Kopp I,Lorenz W,Schulz KD,Wagner U

    更新日期:2006-12-01 00:00:00

  • Characterization of a novel germline BRCA1 splice variant, c.5332+4delA.

    abstract:PURPOSE:Germline mutations in BRCA1 and BRCA2 confer a significant increase in risk for cancer, and determining pathogenicity of a BRCA variant can guide the clinical management of the disease. About 1/3 of BRCA1 variants reported in the public databases have uncertain clinical significance due to lack of conclusive ev...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Yang C,Jairam S,Amoroso KA,Robson ME,Walsh MF,Zhang L

    更新日期:2018-04-01 00:00:00

  • The effect of an aerobic exercise bout 24 h prior to each doxorubicin treatment for breast cancer on markers of cardiotoxicity and treatment symptoms: a RCT.

    abstract:PURPOSE:In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms. METHODS:Twenty-fou...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,随机对照试验


    authors: Kirkham AA,Eves ND,Shave RE,Bland KA,Bovard J,Gelmon KA,Virani SA,McKenzie DC,Stöhr EJ,Waburton DER,Campbell KL

    更新日期:2018-02-01 00:00:00

  • The model-based cost-effectiveness analysis of 1-year adjuvant trastuzumab treatment: based on 2-year follow-up HERA trial data.

    abstract:BACKGROUND:Several randomized controlled trials have confirmed the usefulness of trastuzumab as an adjuvant therapy for HER2-overexpressed breast cancer patients; however, the costs for 1-year treatment are high. Therefore, we performed an economic analysis regarding the efficient distribution of medical resources. ME...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Shiroiwa T,Fukuda T,Shimozuma K,Ohashi Y,Tsutani K

    更新日期:2008-06-01 00:00:00

  • A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer.

    abstract::The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods extend standard pairwise meta-analysis to allow simultaneous comparison of multiple treatments while maintaining ran...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,meta分析


    authors: Generali D,Venturini S,Rognoni C,Ciani O,Pusztai L,Loi S,Jerusalem G,Bottini A,Tarricone R

    更新日期:2015-07-01 00:00:00

  • Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue.

    abstract::Breast cancer is one of the most common cancers in women. The laboratory rat treated with strong carcinogen is the most commonly used animal model for study of breast cancer. Transgenic mouse lines with homologues of human breast cancer oncogenes have been developed. The transgenic mouse line TG.NK with c-neu, the hum...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Rao GN,Ney E,Herbert RA

    更新日期:1997-09-01 00:00:00

  • CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer.

    abstract::Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms with respect to their potential to predict a pathologic complet...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Marmé F,Werft W,Walter A,Keller S,Wang X,Benner A,Burwinkel B,Sinn P,Hug S,Sohn C,Bretz N,Moldenhauer G,Rupp C,Rupp AK,Biakhov MY,Bottini A,Friedrichs K,Khailenko VA,Manikhas GM,Ruiz A,Sánchez-Rovira P,Santoro A

    更新日期:2012-04-01 00:00:00

  • A family-based genetic association study of variants in estrogen-metabolism genes COMT and CYP1B1 and breast cancer risk.

    abstract::In this paper, we report findings from a family-based association study examining the association between polymorphisms in two key estrogen-metabolism genes CYP1B1 (codon 432 G --> C and codon 453 A --> G variants) and COMT (codon 158 G --> A variant) and female breast cancer. We conducted the study among 280 nuclear ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Ahsan H,Chen Y,Whittemore AS,Kibriya MG,Gurvich I,Senie RT,Santella RM

    更新日期:2004-05-01 00:00:00

  • Chlorpheniramine inhibits the synthesis of ornithine decarboxylase and the proliferation of human breast cancer cell lines.

    abstract::Proliferation of both mouse and human breast cancer cells was inhibited by chlorpheniramine (CPA) in a dose-response manner. At the beginning of the exponential phase of growth (two days after seeding), 250 microM CPA was able to reduce cell proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7 cultures). ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Medina MA,García de Veas R,Morata P,Lozano J,Sánchez-Jiménez F

    更新日期:1995-08-01 00:00:00

  • Cyclin-dependent kinase 4 and 6 inhibitors in hormone receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer: a meta-analysis of randomized clinical trials.

    abstract:BACKGROUND:Breakthrough progress has been made in Cyclin-Dependent kinase 4 and 6 (CDK4/6) inhibitors when combined with endocrine therapy (ET) for hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Though significant improvements of progression-free survival (PFS) for CDK4/6 inhibitor...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,meta分析,评审


    authors: Li J,Fu F,Yu L,Huang M,Lin Y,Mei Q,Lv J,Wang C

    更新日期:2020-02-01 00:00:00

  • Prognostic significance of gene-specific promoter hypermethylation in breast cancer patients.

    abstract::The association between promoter methylation status and survival was investigated in a large cohort of women with breast cancer, participants in the Long Island Breast Cancer Study Project. Archived tumor tissues (n = 839) were collected from women diagnosed with a first primary invasive or in situ breast cancer in 19...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Cho YH,Shen J,Gammon MD,Zhang YJ,Wang Q,Gonzalez K,Xu X,Bradshaw PT,Teitelbaum SL,Garbowski G,Hibshoosh H,Neugut AI,Chen J,Santella RM

    更新日期:2012-01-01 00:00:00

  • A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer.

    abstract::Heat shock protein 90 (Hsp90) facilitates maturation and stability of HER2. Combining an Hsp90 inhibitor and trastuzumab has demonstrated anti-tumor effects in patients with HER2+ breast cancer. Adults with measurable, locally advanced or metastatic HER2+ breast cancer and prior trastuzumab treatment were enrolled in ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,多中心研究


    authors: Modi S,Saura C,Henderson C,Lin NU,Mahtani R,Goddard J,Rodenas E,Hudis C,O'Shaughnessy J,Baselga J

    更新日期:2013-05-01 00:00:00

  • Growth kinetics of four human breast carcinomas grown in nude mice.

    abstract::The immune-deficient nude mouse with human tumor xenografts is an appropriate model system for performing detailed growth kinetic examinations. In the present study one estrogen and progesterone receptor-negative (T60) and three receptor-positive (Br-10, MCF-7, T61) human breast cancer xenografts in nude mice were inv...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Spang-Thomsen M,Rygaard K,Hansen L,Halvorsen AC,Vindeløv LL,Brünner N

    更新日期:1989-11-01 00:00:00

  • Current status of paclitaxel in the treatment of breast cancer.

    abstract::Paclitaxel is a highly active single agent as therapy for previously untreated as well as doxorubicin-refractory metastatic breast cancer, with associated response rates of 62% and 20-48%, respectively. Complete responses with paclitaxel occur chiefly in breast cancer patients whose metastatic disease has not been pre...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,评审


    authors: O'Shaughnessy JA,Cowan KH

    更新日期:1995-01-01 00:00:00