Abstract:
: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.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
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 ACdoi
10.1007/s10549-011-1413-6subject
Has Abstractpub_date
2011-05-01 00:00:00pages
153-62issue
1eissn
0167-6806issn
1573-7217journal_volume
127pub_type
杂志文章abstract::Steroid receptor coactivators are important in regulating the function of the receptors in endocrine organ development and in cancers, including breast. Androgen receptor (AR) coactivator ARA70, was first identified as a gene fused to the ret oncogene and later characterized as an AR coactivator. We previously reporte...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1131-5
更新日期:2011-07-01 00:00:00
abstract::We investigated the expression of -CXC chemokine ligand 13 (CXCL13) and its receptor -CXC chemokine receptor 5 (CXCR5) in 98 breast cancer (BC) patients with infiltrating duct carcinoma, out of which 56 were found lymph node metastasis (LNM) positive. Interestingly, co-expression of CXCL13 and CXCR5 showed a significa...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2811-8
更新日期:2014-01-01 00:00:00
abstract::To assess the impact of patient-provider communication on adherence to tamoxifen (TAM) and aromatase inhibitors (AIs) 36 months after breast cancer (BC) diagnosis in a low-income population of women. California statewide surveys were conducted among 921 low-income women with BC at 6, 18, and 36 months after BC diagnos...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2387-8
更新日期:2013-02-01 00:00:00
abstract::Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women in...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s10549-009-0309-1
更新日期:2009-10-01 00:00:00
abstract::CH50, a recombinant CBD-HepII polypeptide of human fibronectin, was shown to suppress tumor metastasis in murine hepatocarcinoma and melanoma models. However, the effect of CH50 on human cancer cells is still not clear. Here we evaluated the efficiency of CH50 delivered by recombinant adeno-associated virus (rAAV) vec...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2783-8
更新日期:2014-01-01 00:00:00
abstract::To evaluate differences in use of sentinel lymph node biopsy (SLNB) by age and race in Medicare recipients with early-stage breast cancer, we examined Surveillance, Epidemiology and End Results-Medicare linked data for women undergoing breast conserving surgery for stage I or II breast cancer, including axillary stagi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1398-1
更新日期:2011-08-01 00:00:00
abstract::Triple-negative breast cancer (TNBC) is a subtype of breast tumor with unique characteristics in terms of clinical-pathological presentation, prognosis, and response to therapy. Epidemiological investigations focusing on the identification of risk factors involved in the onset and progression of TNBCs have identified ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-012-2339-3
更新日期:2013-01-01 00:00:00
abstract::Erratum to: Breast Cancer Res Treat (2013),138:369–381,DOI 10.1007/s10549-012-2389-6. In the original publication of the article, the Fig. 4c and d were published erroneously. The revised Fig. 4 is given in this erratum. ...
journal_title:Breast cancer research and treatment
pub_type: 已发布勘误
doi:10.1007/s10549-016-3752-9
更新日期:2016-04-01 00:00:00
abstract::Several independent randomized controlled trials are initiated to investigate whether sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients with negative axillary ultrasound findings, who are treated with breast conserving therapy. A consequence of omitting sentinel lymph ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-013-2822-5
更新日期:2014-02-01 00:00:00
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
doi:10.1007/s10549-012-1968-x
更新日期:2012-07-01 00:00:00
abstract:PURPOSE:Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs it...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4380-8
更新日期:2017-10-01 00:00:00
abstract::Clinical evidence indicates that higher levels of estrogen receptor beta (ERbeta) predicts improved disease-free and overall survival in patients treated with adjuvant tamoxifen therapy. To better understand the mechanisms in which ERbeta can modulate breast cancer therapies, we introduced ERbeta under an inducible pr...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9640-6
更新日期:2008-05-01 00:00:00
abstract::We investigated the role of glial cell line-derived neurotrophic factor (GDNF) in compensating trastuzumab (TZMB)-induced apoptosis in HER2+ breast cancer (BC) cells using xenograft tumors. We generated BC xenografts in nude mice using samples from three patients selected based on their HER2 status and response to TZM...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-4078-3
更新日期:2017-04-01 00:00:00
abstract::Although younger women with breast cancer have the most to gain from receipt of optimal care, few data are available regarding their receipt of locoregional breast cancer treatments. We identified 317,596 women aged 18-64 who were diagnosed with invasive breast cancer at hospitals reporting to the National Cancer Data...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2156-8
更新日期:2012-10-01 00:00:00
abstract::Experimental evidence suggests an important role of the type I IGF receptor (IGF-IR) in breast cancer development. Breast tumors and breast cancer cell lines express the IGF-IR. IGF-IR levels are higher in cancer cells than in normal breast tissue or in benign mammary tumors. The ligands of the IGF-IR are potent mitog...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/a:1005907101686
更新日期:1998-02-01 00:00:00
abstract::Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a si...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2844-7
更新日期:2014-02-01 00:00:00
abstract::To further clarify risk factors for breast cancer in Japanese women, a self-administered questionnaire was completed by 157 cases with histologically confirmed breast cancer from 1989 to 1993 and by 369 age and residential area matched controls in Gifu, Japan. Conditional logistic regression model was used to assess t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005745824388
更新日期:1997-03-01 00:00:00
abstract::The polypeptide hormone prolactin (Prl), acting through its cell surface receptors, promotes growth and differentiation in normal and malignant breast cells. We demonstrate herein that two Prl-responsive cell lines, NOG-8 normal mouse mammary epithelial and T47D human breast cancer cells, respond to Prl by rapid and t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806209
更新日期:1996-01-01 00:00:00
abstract::Breast cancer cells (BCC) frequently metastasize to bone where they may cause tumor-induced osteolysis (TIO). While the important eroding role of the osteoclasts in TIO is well admitted, the possibility that BCC and/or osteoblasts activated by tumoral factors could also directly degrade bone matrix in this pathology h...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006408916224
更新日期:2000-05-01 00:00:00
abstract:PURPOSE:The RAS family comprises three proto-oncogenes (H-RAS, K-RAS, and N-RAS) and is among the most widely studied of oncogenes. The present study aimed at investigating the clinical relevance of mRNA levels of the three isoforms in a large group of breast cancer patients with a long-term follow-up. METHODS:198 pre...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05474-8
更新日期:2020-01-01 00:00:00
abstract::Previous investigations into the relationship of CAG-repeat lengths in the androgen receptor (AR) gene to female breast cancer (BC) have yielded somewhat confusing results. Decreased AR transactivational activity lowers androgen:estrogen balance, and may thereby effect functional hyperestrogenicity. This may promote t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1012942910375
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:This study aimed to identify and classify genetic variants in consensus moderate-to-high-risk predisposition genes associated with Hereditary Breast and Ovarian Cancer Syndrome (HBOC), in BRCA1/2-negative patients from Brazil. METHODS:The study comprised 126 index patients who met NCCN clinical criteria and te...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05985-9
更新日期:2020-10-30 00:00:00
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
doi:10.1007/BF01810740
更新日期:1989-11-01 00:00:00
abstract::Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains of immune-deficient m...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01833265
更新日期:1993-01-01 00:00:00
abstract::To explain a bimodal relapse hazard among early stage breast cancer patients treated by mastectomy we postulated that relapses within 4 years of surgery resulted from something that happened at about the time of surgery to provoke sudden exits from dormant phases to active growth. Relapses at 10 months appeared to be ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2094-5
更新日期:2012-07-01 00:00:00
abstract::Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3608-8
更新日期:2015-11-01 00:00:00
abstract::Expression of HOX transcript antisense intergenic RNA (HOTAIR)--a long non-coding RNA--has been examined in a variety of human cancers, and overexpression of HOTAIR is correlated with poor survival among breast, colon, and liver cancer patients. In this retrospective study, we examine HOTAIR expression in 164 primary ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2776-7
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Vinorelbine (Navelbin; N) has proven to be active in patients with advanced breast cancer (ABC) and cyclophosphamide (C) and epirubicin (Epiadriamycin: E) are still among the main cytostatic agents against this tumor. On this basis was carried out a study to determine the activity and toxicity of the combina...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/a:1006477109230
更新日期:2000-07-01 00:00:00
abstract::Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status an...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2439-8
更新日期:2013-04-01 00:00:00
abstract::We have measured the levels of tamoxifen and three of its metabolites in the blood of patients receiving tamoxifen alone or combination therapy with tamoxifen and medroxyprogesterone acetate. Our results indicate that addition of the progestogen significantly alters the metabolism of tamoxifen over a six-month period....
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01833345
更新日期:1992-01-01 00:00:00