Long-term cardiac safety and outcomes of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab with and without lapatinib in patients with early breast cancer.

Background: The authors have previously reported 2 consecutive phase 2 trials in patients with early breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2) to assess the feasibility of incorporating anti-HER2 therapies into dose-dense (dd) chemotherapy regimens. The incidence of congestive heart failure (CHF) at a median follow-up of 2 years was 1.4% and 3.

Phase II trial of saracatinib (AZD0530), an oral SRC-inhibitor for the treatment of patients with hormone receptor-negative metastatic breast cancer.

Background: SRC activation is associated with cell migration, proliferation, and metastasis. Saracatinib is an oral tyrosine kinase inhibitor (TKI) selective for SRC. We performed this trial to evaluate the efficacy and safety of saracatinib monotherapy in patients with estrogen receptor (ER)(-) and progesterone receptor (PR)(-) metastatic breast cancer (MBC).

A phase I study of dasatinib and weekly paclitaxel for metastatic breast cancer.

Background: SRC plays an important role in the pathogenesis of metastatic breast cancer (MBC). In preclinical models, paclitaxel and the oral SRC inhibitor dasatinib showed greater antitumor activity than either agent. To determine the maximum tolerated dose of this combination, we conducted a phase I study.

Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib.

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.

Dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in HER2/neu-overexpressed/amplified breast cancer is not feasible because of excessive diarrhea.

Purpose: Dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel and trastuzumab (PT) is feasible. Lapatinib is effective in the treatment of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer. We conducted a pilot study of dose-dense AC followed by PT plus lapatinib (PTL) followed by trastuzumab plus lapatinib (TL).