Liposomal Doxorubicin and Docetaxel in HER2 Negative Metastatic Breast Cancer

Phase II non comparative study, assessing the safety (primarily cardiac safety) and efficacy in patients with locally advanced or metastatic HER2/neu negative breast cancer not yet treated with chemotherapy for metastatic disease.

Myocet and Taxotere will be given for a maximum of 6 cycles. Endpoints: cardiotoxicity (left ventricular ejection fraction decrease and/or symptoms of heart failure), serious other toxicity, disease progression.

Inclusion criteria

• Women with histologically documented metastatic or locally advanced metastatic HER2/neu negative breast cancer.
• In the case of previous adjuvant or neoadjuvant chemotherapy with anthracyclines or taxanes, this must have been completed more than 12 months before inclusion.
• In the case of previous adjuvant or neoadjuvant chemotherapy, cumulative anthracycline dose ≤ 360 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin or 75 mg/m2 of mitoxantrone on inclusion.
• Previous endocrine therapy is authorized (endocrine therapy other than goserelin must be stopped before starting treatment).
• Previous radiotherapy is authorized, if discontinued ≥ 4 weeks prior to inclusion in the study and if < 10% of the bone marrow was within the irradiated area.
• Age ≥ 18 years.
• Performance status 0,1, or 2.
• Life expectancy ≥ 3 months.
• Evaluable disease.
• Normal LVEF (multigated acquisition [MUGA] scan or echocardiography).
• Normal haematological, hepatic and renal parameters: neutrophils ≥ 1.5 x 10^9/l; platelets ≥ 100 x 10^9/l; hemoglobin (Hb) ≥ 6 mmol/L; total bilirubin ≤ 1.5 times the upper limit of normal (ULN); transaminases ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 x ULN; creatinine ≤ 1.5 x ULN.
• Dated and signed written informed consent.

Exclusion criteria

• Previous chemotherapy for metastatic disease.
• History of other cancer, except for cervical carcinoma in situ treated by cone resection or basal cell or squamous cell skin cancer.
• History of congestive heart failure or myocardial infarction ≤ 1 year; cardiac function: NYHA ≥ 2 or LVEF < 50%. Uncontrolled significant heart disease, such as unstable angina.
• Poorly controlled hypertension.
• Performance status 3, 4.
• Symptomatic or progressive brain metastases.
• Active infection or other serious underlying disease.
• Concomitant participation in other clinical trials.
• Pregnant women or nursing mothers; patients of childbearing potential without effective contraception.
• Absolute medical contraindication to the use of corticosteroid premedication.
• Allergy to polysorbate 80, doxorubicin, or egg lecithin.
• NCI-CTC grade > 1 peripheral neuropathy.
• Patients not able to comply with regular medical follow-up