A phase II study of trastuzumab and capecitabine for patients with HER2-overexpressing metastatic breast cancer: Japan Breast Cancer Research Network (JBCRN) 00 Trial

Yamamoto, Daigo; Iwase, Satoru; Kitamura, Kenichiro; Odagiri, Hiroki; Yamamoto, Chizuko; Nagumo, Yoshinori

doi:10.1007/s00280-007-0497-5

Cited by 50 publications

(32 citation statements)

References 18 publications

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“…Although the response rate was similar to that seen in more heavily pretreated disease, time-related endpoints were more favorable and were consistent with findings from a randomized, phase III trial of capecitabine monotherapy in the first-line setting. Two recently reported phase II studies have demonstrated high activity when the capecitabine regimen evaluated in our study is given in combination with trastuzumab in patients with HER2-positive MBC [21,22] , indicating that capecitabine is active irrespective of schedule and HER2 status.…”

Section: Discussionsupporting

confidence: 52%

Study of Low-Dose Capecitabine Monotherapy for Metastatic Breast Cancer

et al. 2010

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Background: Capecitabine is an established therapy for metastatic breast cancer. In Japan, a 4 weekly regimen is often used, but data for this schedule in the first-line setting are lacking. Methods: Metastatic breast cancer patients who had received no chemotherapy for recurrent disease received capecitabine 825 mg/m² twice daily, on days 1–21 of a 28-day cycle until disease progression or unacceptable toxicity. The primary endpoint was response rate. Results: In 33 eligible patients, median age was 53 years (range 27–73). Prior adjuvant therapy included an anthracycline in 90% and a taxane in 40%. The response rate was 18%; a further 24% had stable disease for ≧6 months. Median progression-free and overall survival were 6.9 and 24.8 months, respectively. The only grade 3 events were neutropenia (6%) and hand-foot syndrome (15%). Conclusions: These preliminary results confirm previous data showing that a lower capecitabine dose is an active and well-tolerated first-line therapy for metastatic breast cancer.

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Section: Discussionsupporting

confidence: 52%

Study of Low-Dose Capecitabine Monotherapy for Metastatic Breast Cancer

et al. 2010

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“…The median PFS and OS ranged from 7 to 12 and 18 to 23 months, respectively. [26][27][28] Combination therapy with trastuzumab and an HER2/neu-specific vaccine warrants further evaluation as a therapeutic regimen. …”

Section: Discussionmentioning

confidence: 99%

Concurrent Trastuzumab and HER2/neu-Specific Vaccination in Patients With Metastatic Breast Cancer

Disis

Wallace

Gooley

et al. 2009

JCO

275

175

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A B S T R A C T PurposeThe primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of combination therapy consisting of concurrent trastuzumab and human epidermal growth factor receptor 2 (HER2)/neu-specific vaccination in patients with HER2/neu-overexpressing metastatic breast cancer. Patients and MethodsTwenty-two patients with stage IV HER2/neu-positive breast cancer receiving trastuzumab therapy were vaccinated with an HER2/neu T-helper peptide-based vaccine. Toxicity was graded according to National Cancer Institute criteria, and antigen specific T-cell immunity was assessed by interferon gamma enzyme-linked immunosorbent spot assay. Data on progression-free and overall survival were collected. ResultsConcurrent trastuzumab and HER2/neu vaccinations were well tolerated, with 15% of patients experiencing an asymptomatic decline in left ventricular ejection fraction below the normal range during combination therapy. Although many patients had pre-existing immunity specific for HER2/neu and other breast cancer antigens while treated with trastuzumab alone, that immunity could be significantly boosted and maintained with vaccination. Epitope spreading within HER2/ neu and to additional tumor-related proteins was stimulated by immunization, and the magnitude of the T-cell response generated was significantly inversely correlated with serum transforming growth factor beta levels. At a median follow-up of 36 months from the first vaccine, the median overall survival in the study population has not been reached. ConclusionCombination therapy with trastuzumab and a HER2/neu vaccine is associated with minimal toxicity and results in prolonged, robust, antigen-specific immune responses in treated patients.

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“…The mechanism of cardiotoxicity caused due to the combined use of trastuzumab and anthracyclines is of particular importance because of the more frequent application of this therapy (7). Since this therapy leads to increased levels of ROS (reactive oxygen particles) and reduction of antioxidant components, it induces oxidative stress that is reflected in the cardiac dysfunction and increased synthesis of angiotensin II that inhibits the activity of the neuroregulin, preventing its binding to the HER receptors, and thus blocks the apoptosis signalling pathways (8). Angiotesin II also affects the activation and regulation of NADPH oxidase by interacting with the G protein linked to the AT 1 receptor, which activates the NADPH oxidase through protein kinase C. NADPH oxidase, in turn, generates free radicals which are potent ROS.…”

Section: Discussionmentioning

confidence: 99%

Significance of Echocardiography in the Assessment of Left Ventricular Function in Patients Receiving Combined Adjuvant Treatment with Anthracyclines and Trastuzumab / Značaj ehokardiografije u proceni funkcije leve komore kod bolesnica na adjuvantnoj terapji (kombinovana terapija antraciklinima i trastuzumabom)

Krstić¹,

Ilic²,

Vrbić³

et al. 2015

Acta Facultatis Medicae Naissensis

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The application of anthracycline and trastuzumab in adjuvant breast cancer treatment approach has significantly improved the survival of patients, but also carries the risk of cardiotoxicity that is manifested by reducing the ejection fraction of the heart. The aim of the study was to investigate the effect of cumulative anthracycline dose in combination therapy with trastuzumab on the left ventricular ejection fraction, and the influence of the time interval for starting the treatment with trastuzumab.The study included a group of 80 breast cancer patients (aged 28 to 75 years) who underwent the therapy with anthracyclines (IV-VI cycles) with the continuation of trastuzumab therapy for a period of one year. Ejection fraction at the end of completing the treatment period (VI anthracycline cycles and trastuzumab) was significantly lower in 68 (93%) patients compared to the value at the beginning of the study (68.2% ± 6.06 to 62.1 ± 6.1%; p <0.0001; difference 6.1%). In five patients (anthracyclines and trastuzumab IV cycles) a decrease of 7.1% EF; p = 0.0043 was registered compared to the baseline values. The reduction in the ejection fraction was highest in patients in whom the trastuzumab therapy was initiated one month after the last anthracycline therapy (7.33%), and lowest in the subgroup who started receiving the therapy after three months (5.31%).In patients on cytostatic therapy, echocardiography proves the reduction in the left ventricular ejection fraction, which is cumulative and dose-dependent, and it also proves that the shorter time interval between the last cycle of anthracycline and the initial trastuzumab treatment the more it is associated with a marked decrease in the left ventricular ejection fraction.

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A phase II study of trastuzumab and capecitabine for patients with HER2-overexpressing metastatic breast cancer: Japan Breast Cancer Research Network (JBCRN) 00 Trial

Abstract: Trastuzumab in combination with capecitabine is highly active in women with HER2-overexpressing metastatic breast cancer and is well tolerated.

Cited by 50 publications

References 18 publications

Study of Low-Dose Capecitabine Monotherapy for Metastatic Breast Cancer

Study of Low-Dose Capecitabine Monotherapy for Metastatic Breast Cancer

Concurrent Trastuzumab and HER2/neu-Specific Vaccination in Patients With Metastatic Breast Cancer

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