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












  • Association of tamoxifen (TAM) and TAM metabolite concentrations with self-reported side effects of TAM in women with breast cancer.

    abstract::The positive effects of tamoxifen (TAM) on breast cancer recurrence and survival as well as on overall mortality have led to its use as the predominant adjuvant therapy among women with breast cancer. However, the association of TAM intake with undesirable side effects has been reported in numerous studies. This analy...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Gallicchio L,Lord G,Tkaczuk K,Danton M,Lewis LM,Lim CK,Flaws JA

    更新日期:2004-05-01 00:00:00

  • Racial differences in the familial aggregation of breast cancer and other female cancers.

    abstract::Although breast cancer familial aggregation has been studied in Caucasians, information for African-Americans is scant. We used family cancer history from the Women's Contraceptive and Reproductive Experiences study to assess the aggregation of breast and gynecological cancers in African-American and Caucasian familie...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Simon MS,Korczak JF,Yee CL,Daling JR,Malone KE,Bernstein L,Marchbanks PA,Folger SG,McDonald JA,Norman SA,Strom BL,Deapen D,Ursin G,Burkman RT,Press MF,Schwartz AG,Spirtas R

    更新日期:2005-02-01 00:00:00

  • Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer.

    abstract:PURPOSE:Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer (LABC). The IBC phenotype is characterized by an infiltrative growth pattern, increased (lymph)angiogenesis and the propensity to invade dermal lymphatics. In pancreatic cancer, interactions between caveolin-1 and Rho...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Van den Eynden GG,Van Laere SJ,Van der Auwera I,Merajver SD,Van Marck EA,van Dam P,Vermeulen PB,Dirix LY,van Golen KL

    更新日期:2006-02-01 00:00:00

  • Chemotherapy responsiveness of human breast tumors in the 6-day subrenal capsule assay: an update.

    abstract::Feasibility of utilizing the 6-day subrenal capsule (SRC) assay to screen drugs against fresh surgical explants of human tumors was confirmed by testing six clinically active chemotherapeutic agents against 141 human breast cancers. Response rates of the six drugs obtained in the assay compared favorably with clinical...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Bogden AE,Costanza ME,Reich SD,Griffin TW,Cobb WR

    更新日期:1983-01-01 00:00:00

  • Recurrence risk perception and quality of life following treatment of breast cancer.

    abstract:PURPOSE:Little is known about different ways of assessing risk of distant recurrence following cancer treatment (e.g., numeric or descriptive). We sought to evaluate the association between overestimation of risk of distant recurrence of breast cancer and key patient-reported outcomes, including quality of life and wor...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Hawley ST,Janz NK,Griffith KA,Jagsi R,Friese CR,Kurian AW,Hamilton AS,Ward KC,Morrow M,Wallner LP,Katz SJ

    更新日期:2017-02-01 00:00:00

  • Characterization of platelet aggregation induced by human breast carcinoma and its inhibition by snake venom peptides, trigramin and rhodostomin.

    abstract::MCF-7 cells, a metastatic human breast carcinoma line, caused dose-dependent platelet aggregation in heparinized human platelet-rich plasma (PRP). MCF-7 tumor cell-induced platelet aggregation (TCIPA) was almost blocked by apyrase (0.5 U/ml) and completely inhibited by hirudin (5 U/ml). This TCIPA was unaffected by cy...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Chiang HS,Swaim MW,Huang TF

    更新日期:1995-03-01 00:00:00

  • Effects of high-intensity interval training on vascular endothelial function and vascular wall thickness in breast cancer patients receiving anthracycline-based chemotherapy: a randomized pilot study.

    abstract:PURPOSE:The purpose of this study was to determine the effects of an 8-week high-intensity interval training (HIIT) intervention on vascular endothelial function, measured as brachial artery flow-mediated dilation (baFMD), and vascular wall thickness measured by carotid intima media thickness (cIMT) in breast cancer pa...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,随机对照试验


    authors: Lee K,Kang I,Mack WJ,Mortimer J,Sattler F,Salem G,Lu J,Dieli-Conwright CM

    更新日期:2019-09-01 00:00:00

  • Efficacy of three potent steroid sulfatase inhibitors: pre-clinical investigations for their use in the treatment of hormone-dependent breast cancer.

    abstract::Estrogenic steroids, such as estradiol, are known to play a crucial role in the development and growth of hormone-dependent breast cancer. Steroid sulfatase (STS) inhibitors that can prevent the biosynthesis of these steroids via the sulfatase pathway offer therapeutic potential. We show here the in vivo profile, incl...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Foster PA,Chander SK,Parsons MF,Newman SP,Woo LW,Potter BV,Reed MJ,Purohit A

    更新日期:2008-09-01 00:00:00

  • The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells.

    abstract::Cell migration is essential in many diverse processes ranging from embryonic development to wound healing and immune response. Cancer cells have recently been shown to utilize chemoattraction mechanisms mediated by chemokines and their respective receptors, e.g., the CXCL12/CXCR4 pathway normally found in leukocytes. ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Schmid BC,Rezniczek GA,Fabjani G,Yoneda T,Leodolter S,Zeillinger R

    更新日期:2007-12-01 00:00:00

  • The expression of gene transcripts of telomere-associated genes in human breast cancer: correlation with clinico-pathological parameters and clinical outcome.

    abstract:BACKGROUND:Telomerase is a ribonucleoprotein enzyme that synthesises telomeres in human germ cells, embryogenesis and in cancer, maintaining chromosomal length, stability and cellular immortality. The hTERT gene is the rate-limiting determinant of telomerase reactivation during immortalization and malignant transformat...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Salhab M,Jiang WG,Newbold RF,Mokbel K

    更新日期:2008-05-01 00:00:00

  • A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer.

    abstract::A dose-response relationship has been suggested for medroxyprogesterone acetate in the treatment of advanced breast cancer. To determine the tolerability and efficacy of increasing doses of megestrol acetate in the treatment of metastatic breast cancer, we conducted a phase I/II study among 57 patients. Three patients...

    journal_title:Breast cancer research and treatment

    pub_type: 临床试验,杂志文章


    authors: Parnes HL,Abrams JS,Tchekmedyian NS,Tait N,Aisner J

    更新日期:1991-08-01 00:00:00

  • Breast cancer subpopulation with high risk of internal mammary lymph nodes metastasis: analysis of 2,269 Chinese breast cancer patients treated with extended radical mastectomy.

    abstract:PURPOSE:The selective treatment of internal mammary lymph nodes (IMNs) in breast cancer is controversial. The purpose of this research was to determine the subpopulation patients with high risk of internal mammary lymph nodes metastasis who received extended radical mastectomy without any preoperative treatment from 19...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Huang O,Wang L,Shen K,Lin H,Hu Z,Liu G,Wu J,Lu J,Shao Z,Han Q,Shen Z

    更新日期:2008-02-01 00:00:00

  • Tamoxifen-induced increases in cytoplasmic free Ca2+ levels in human breast cancer cells.

    abstract::Tamoxifen has been shown to increase cytoplasmic free Ca2+ levels [Ca2+]i in renal tubular cells and bladder cancer cells, and to after Ca2+ signaling in MCF-7 breast cancer cells. The present study examined the effect of tamoxifen on [Ca2+], in ZR-75-1 human breast cancer cells using fura-2 as an indicator. Tamoxifen...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Chang HT,Huang JK,Wang JL,Cheng JS,Lee KC,Lo YK,Liu CP,Chou KJ,Chen WC,Su W,Law YP,Jan CR

    更新日期:2002-01-01 00:00:00

  • Analyzing non-sentinel axillary metastases in patients with T3-T4 cN0 early breast cancer and tumor-involved sentinel lymph nodes undergoing breast-conserving therapy or mastectomy.

    abstract:PURPOSE:In the ACOSOG Z0011 trial, completing axillary lymph node dissection (cALND) did not benefit patients with T1-T2 cN0 early breast cancer and 1-2 positive sentinel lymph nodes (SLN) undergoing breast-conserving surgery (BCT). This paper reports cALND rates in the clinical routine for patients who had higher (T3-...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Riedel F,Heil J,Feisst M,Moderow M,von Au A,Domschke C,Michel L,Schaefgen B,Golatta M,Hennigs A

    更新日期:2020-11-01 00:00:00

  • Ras-related protein 1 and the insulin-like growth factor type I receptor are associated with risk of progression in patients diagnosed with carcinoma in situ.

    abstract::Currently, there are no applied molecular markers to aid in predicting risk of carcinoma in situ (CIS) progression to invasive cancer, and therefore, all women diagnosed with CIS undergo surgery. Standard assessment of protein expression in fixed tissue by immunohistochemistry (IHC) is not quantitative and hence is no...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Furstenau DK,Mitra N,Wan F,Lewis R,Feldman MD,Fraker DL,Guvakova MA

    更新日期:2011-09-01 00:00:00

  • Status of estrogen receptor 1 (ESR1) gene in mastopathy predicts subsequent development of breast cancer.

    abstract::Mastopathy is a common disease of the breast likely associated with elevated estrogen levels and a putative risk factor for breast cancer. The role of estrogen receptor alpha (ESR1) in mastopathy has not been investigated previously. Here, we investigated the prevalence of ESR1 gene amplification in mastopathy and its...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Soysal SD,Kilic IB,Regenbrecht CR,Schneider S,Muenst S,Kilic N,Güth U,Dietel M,Terracciano LM,Kilic E

    更新日期:2015-06-01 00:00:00

  • Structural and functional studies of insulin receptors in human breast cancer.

    abstract::We characterized the structure and the function of insulin receptors isolated from 10 human breast cancer specimens. We observed that the insulin receptor content, as determined by a specific radioimmunoassay, was four fold increased in human breast cancer tissue when compared to normal breast tissues. In both cancer ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Frittitta L,Vigneri R,Papa V,Goldfine ID,Grasso G,Trischitta V

    更新日期:1993-01-01 00:00:00

  • Breast sarcomas and malignant phyllodes tumours: comparison of clinicopathological features, treatment strategies, prognostic factors and outcomes.

    abstract::We aimed to compare the clinicopathological features, treatment strategies and clinical outcomes of breast sarcomas (BS) and malignant phyllodes tumours (MPT), and determine their prognostic factors. Cases of BS and MPT diagnosed at the Department of Pathology, Singapore General Hospital from January 1991 to December ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Lim SZ,Selvarajan S,Thike AA,Nasir ND,Tan BK,Ong KW,Tan PH

    更新日期:2016-09-01 00:00:00

  • Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate.

    abstract::Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12-dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co-glycolide] ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Li S,Lepage M,Mérand Y,Bélanger A,Labrie F

    更新日期:1992-01-01 00:00:00

  • Differential presentation and survival of de novo and recurrent metastatic breast cancer over time: 1990-2010.

    abstract:BACKGROUND:Differences in de novo (dnMBC) and recurrent metastatic breast cancer (rMBC) presentation and survival over time have not been adequately described. METHODS:A retrospective cohort study, 1990-2010, with follow up through 2015 of dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distan...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Malmgren JA,Mayer M,Atwood MK,Kaplan HG

    更新日期:2018-01-01 00:00:00

  • Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers.

    abstract::The mutation pattern of breast cancer molecular subtypes is incompletely understood. The purpose of this study was to identify mutations in genes that may be targeted with currently available investigational drugs in the three major breast cancer subtypes (ER+/HER2-, HER2+, and Triple Negative). We extracted DNA from ...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Santarpia L,Qi Y,Stemke-Hale K,Wang B,Young EJ,Booser DJ,Holmes FA,O'Shaughnessy J,Hellerstedt B,Pippen J,Vidaurre T,Gomez H,Valero V,Hortobagyi GN,Symmans WF,Bottai G,Di Leo A,Gonzalez-Angulo AM,Pusztai L

    更新日期:2012-07-01 00:00:00

  • Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis.

    abstract::Obesity is a risk factor for the development of new cases of breast cancer and also affects survival in women who have already been diagnosed with breast cancer. Early studies of obesity and breast cancer survival have been summarised in two meta-analyses, but the latest of these only included studies that recruited w...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,meta分析,评审


    authors: Protani M,Coory M,Martin JH

    更新日期:2010-10-01 00:00:00

  • Cellular localisation by in situ hybridisation of cathepsin D, stromelysin 3, and urokinase plasminogen activator RNAs in breast cancer.

    abstract::We have compared by RNA in situ hybridisation on serial cryo-sections the distribution of cathepsin D (cathD), stromelysin 3 (strom-3), and urokinase plasminogen activator (UPA) gene expression in different tissues of human benign and malignant mammary tumors. Cath-D expression was found to be higher in adenocarcinoma...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Escot C,Zhao Y,Puech C,Rochefort H

    更新日期:1996-01-01 00:00:00

  • Carboplatin plus taxanes are non-inferior to epirubicin plus cyclophosphamide followed by taxanes as adjuvant chemotherapy for early triple-negative breast cancer.

    abstract:PURPOSE:Platinum plays an important role in the treatment of triple-negative breast cancer (TNBC) in neoadjuvant and metastatic settings. However, its role in an adjuvant setting remains unclear. METHODS:In this non-inferior randomized phase 2 trial, we randomly assigned 308 chemotherapy-naive patients with histologic...

    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: Du F,Wang W,Wang Y,Li M,Zhu A,Wang J,Cai R,Ma F,Fan Y,Li Q,Zhang P,Todorovic V,Yuan P,Xu B

    更新日期:2020-07-01 00:00:00

  • Breast cancer prevention through modulation of endogenous hormones.

    abstract::The use of exogenous sex-steroids for hormonal contraception is important to the way of life of many modern women. The widespread use of hormonal contraceptives represents a unique opportunity to have a substantial positive impact on women's health. The observation that users of oral combination type contraceptives ha...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,评审


    authors: Spicer DV,Pike MC

    更新日期:1993-11-01 00:00:00

  • A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7.

    abstract::Bone morphogenetic proteins (BMPs) regulate diverse cellular processes, such as proliferation, differentiation, and apoptosis. The BMPs have been studied in several cancers, but thus far contradictory results have been obtained and, especially in breast cancer, information on BMPs is still limited. We performed a syst...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Alarmo EL,Kuukasjärvi T,Karhu R,Kallioniemi A

    更新日期:2007-06-01 00:00:00

  • Relationship between IHC4 score and response to neo-adjuvant chemotherapy in estrogen receptor-positive breast cancer.

    abstract:AIMS:To determine whether IHC4 score assessed on pre-treatment core biopsies (i) predicts response to neo-adjuvant chemotherapy in ER-positive (ER+) breast cancer; (ii) provides more predictive information than Ki67 alone. METHODS:113 patients with ER+ primary breast cancer treated with neo-adjuvant chemotherapy at th...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章


    authors: Sheri A,Smith IE,Hills M,Jones RL,Johnston SR,Dowsett M

    更新日期:2017-07-01 00:00:00

  • Insulin-like growth factor expression in breast cancer epithelium and stroma.

    abstract::The insulin-like growth factors (IGFs) are mitogens for many cancer cell types. In breast cancer cells, IGF-I and IGF-II have both been shown to stimulate cell proliferation. However, IGF-I mRNA has not been found in human breast cancer cell lines, making it unlikely that IGF-I is commonly expressed as an autocrine gr...

    journal_title:Breast cancer research and treatment

    pub_type: 杂志文章,评审


    authors: Cullen KJ,Allison A,Martire I,Ellis M,Singer C

    更新日期:1992-01-01 00:00:00

  • Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2-negative breast cancer: NSABP Foundation Study FB-9.

    abstract::Locally advanced breast cancer (LABC) is a good setting in which to monitor response to neoadjuvant chemotherapy, to downsize the tumor (which facilitates breast-conserving surgery), and to test newer agents in untreated patients. Eribulin (E) has shown activity in patients who have undergone previous taxane, anthracy...

    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: Abraham J,Robidoux A,Tan AR,Limentani S,Sturtz K,Shalaby I,Alcorn H,Buyse ME,Wolmark N,Jacobs SA

    更新日期:2015-07-01 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