The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Trastuzumab in HER-2/<i>neu</i> Overexpressed/Amplified Breast Cancer

Dang, Chau T.; Fornier, Monica; Sugarman, Steven; Troso-Sandoval, Tiffany A.; Lake, Diana; D’Andrea, Gabriella; Seidman, Andrew D.; Sklarin, Nancy T.; Dickler, Maura N.; Currie, Violante E.; Gilewski, Theresa; Moynahan, Mary Ellen; Drullinsky, Pamela; Wasserheit-Leiblich, Carolyn; Nl, Mills; Steingart, Richard M.; Panageas, Katherine S.; Norton, Larry; Hudis, Clifford A.

doi:10.1200/jco.2007.12.0733

Cited by 58 publications

(52 citation statements)

References 22 publications

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“…Subsequently, we demonstrated that ddAC followed by paclitaxel (P) with T was associated with an overall CHF rate of 1.4% (1/70 patients; ref. 6). Taken together, these findings suggest that dd anthracycline-based chemotherapy incorporating T is associated with a low risk of cardiotoxicity.…”

Section: Introductionmentioning

confidence: 75%

Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib

Morris

Chen

Steingart

et al. 2011

Clinical Cancer Research

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131

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Purpose: There are no validated methods of early detection of cardiotoxicity from trastuzumab (T) following anthracycline-based chemotherapy. Currently changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Within a prospective feasibility study of dose-dense (dd) doxorubicin and cyclophosphamide (AC) ! weekly paclitaxel (P) with T and lapatinib (L), we included a preplanned analysis of correlative cardiac Troponin I (cTnI) and C-reactive protein (CRP) as early biomarkers of cardiotoxicity.Experimental Design: As previously described, patients received ddACx 4!PTL!TL. LVEF was assessed at months 0, 2, 6, 9, and 18 and cTnI and CRP measured every 2 weeks during chemotherapy then at months 6, 9, and 18. These biomarkers were correlated with changes in LVEF.Results: Ninety-five patients enrolled. Overall, 3 (3%) patients withdrew during AC and 41 (43%) withdrew during PTL!TL, mostly due to diarrhea. Median LVEF was 68% (baseline), 69% (month 2), 65% (month 6), 65% (month 9), and 65% (month 18). The majority (67%) had a detectable cTnI during the study. The proportion of detectable cTnIs increased over time; 4% at baseline, 11% at month 2, and 50% at month 3. The timing of these detectable cTnIs preceded maximum-recorded decline in LVEF. However, overall, maximum cTnI levels did not correlate with LVEF declines. A detectable CRP was seen in 74/95 (78%) but did not correlate with LVEF declines.Conclusion: In patients receiving ddAC!PTL, cTnIs are commonly detected. These elevations may precede changes in LVEF but, as assessed in this trial, do not predict CHF.

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Section: Introductionmentioning

confidence: 75%

Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib

Morris

Chen

Steingart

et al. 2011

Clinical Cancer Research

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131

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“…Combining dose-dense AC and paclitaxel with HER2-targeted therapy appears to be safe from a cardiac point of view, and toxicity does not seem to be increased in relation to previous non-dose-dense HER2 clinical trials [32,33,34]. This makes sense if we consider that no trial has shown increased cardiac risk with reduced anthracycline intervals [21,22,25,28].…”

Section: Special Populations and Final Remarksmentioning

confidence: 98%

Adjuvant Dose-Dense Chemotherapy for Breast Cancer: Available Evidence and Recent Updates

Almeida

Rosa

2018

Breast Care

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Adjuvant chemotherapy has greatly improved the prognosis of early breast cancer. Dose-dense chemotherapy seeks to increase efficacy by changing the interval between cycles of treatment without the need of increasing doses and toxicity. According to the Gompertzian model, the smaller tumors are and the more rapid they grow, the more benefit could be expected from dose-dense therapy. Some clinical trials showed reduced mortality when adjuvant chemotherapy is administered in shorter intervals, while others had discordant results. Interpreting results is difficult due to a great variability in doses and schemes used in different trials. Dose-dense chemotherapy does not seem to increase adverse events and appears to be the most efficacious in higher-risk individuals and in hormone receptor-negative tumors. This review intends to summarize the available evidence and recent research about this subject.

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“…In this trial, a significant benefit was found for the dose-dense group. Based upon those results and confirmatory data [33,34], dose-dense regimens are today deemed standard in North America. Likely independent of G-CSF support, a just recently observed potential drawback of dosedense treatment is a decline in pulmonary function, as defined by a significant reduction of carbon monoxide diffusion capacity [35].…”

Section: Studies Of G-csf In Breast Cancermentioning

confidence: 87%

The Role of Supportive Therapy in the Era of Modern Adjuvant Treatment – Current and Future Tools

Bartsch

Steger²

2009

Breast Care

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Recent advances in adjuvant treatment of breast cancer have improved progression-free and overall survival. Optimal management of treatment-induced side effects has therefore gained further importance. This review cannot provide a comprehensive overview of treatment-related toxicity and its management, but focuses on important new developments in the field of supportive therapy. Erythropoietins, while highly effective in treating chemotherapy-induced anaemia, may have detrimental effects on outcome, and should only be used with the aim to reduce the number of whole blood transfusions. Granulocyte colony-stimulating factors were a prerequisite for development of dose-dense regimens, and are also necessary in many anthracycline/taxane combination regimens. A potential tumour-stimulating effect was not proven in solid cancers. For side effects of conventional chemotherapy, such as mucositis, nausea, or diarrhoea, regularly updated guidelines may improve symptom control. Overall, modern supportive treatment tools will further reduce treatment-related mortality and help increase quality of life.

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The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Trastuzumab in HER-2/neu Overexpressed/Amplified Breast Cancer

Abstract: Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.

Cited by 58 publications

References 22 publications

Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib

Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib

Adjuvant Dose-Dense Chemotherapy for Breast Cancer: Available Evidence and Recent Updates

The Role of Supportive Therapy in the Era of Modern Adjuvant Treatment – Current and Future Tools

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The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Trastuzumab in HER-2/neu Overexpressed/Amplified Breast Cancer

Abstract: Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.

Cited by 58 publications

References 22 publications

Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib

Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib

Adjuvant Dose-Dense Chemotherapy for Breast Cancer: Available Evidence and Recent Updates

The Role of Supportive Therapy in the Era of Modern Adjuvant Treatment &ndash; Current and Future Tools

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Product

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The Role of Supportive Therapy in the Era of Modern Adjuvant Treatment – Current and Future Tools