Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer

Phase II Study of Dose-Dense Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/NEU-Overexpressed/Amplified Breast Cancer: Feasibility

The purpose of this study is to study a new treatment for HER-2/neu (+) breast cancer.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

  • Bilateral synchronous breast tumors allowed

  • Any nodal status or tumor size allowed

    • No stage IV disease

• HER2/neu-positive disease

  • 3+ by IHC OR FISH-amplified

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Male or female

• Menopausal status not specified

• ECOG performance status 0-1

• Absolute neutrophil count ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³

• Bilirubin ≤ 1.1 mg/dL

• SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception during and after completion of study therapy

• LVEF ≥ 50% by MUGA scan

• No peripheral neuropathy > grade 1

• No active second malignancy within the past 5 years except for adequately treated nonmelanoma skin cancer or in situ carcinoma of the cervix

• No known allergy or hypersensitivity to doxorubicin hydrochloride, cyclophosphamide, paclitaxel, or other drugs formulated in Cremophor EL

• No psychiatric illness or concurrent medical conditions that would preclude study treatment

• No other conditions, including any of the following:

  • Unstable angina
  • Congestive heart failure
  • Myocardial infarction within the past 12 months
  • High-risk uncontrolled arrhythmias (e.g., ventricular tachycardia, high-grade AV block, or supraventricular arrhythmias that are not adequately controlled)

• No QT prolongation (> 500 ms)

• No active unresolved infections

• No sensitivity to E. coli derived proteins

PRIOR CONCURRENT THERAPY:

• Prior hormonal therapy for chemoprevention allowed
• No prior trastuzumab (Herceptin®)
• No prior anthracyclines
• No concurrent hormonal therapy, including hormonal contraception (e.g., birth control pills or ovarian hormonal or replacement therapy)
• No other concurrent chemotherapy, radiotherapy, immunotherapy, or biotherapy for breast cancer
• No concurrent drugs that may prolong the QT