liposomal doxorubicin, trastuzumab, and docetaxel in her2 positive metastatic breast cancer

Conditions: Breast Cancer; Neoplasm Metastasis

Summary: this is an open phase ii study evaluating the efficacy and safety of the non pegylated liposomal doxorubicin (myocet®), trastuzumab (herceptin®), and docetaxel (taxotere®) combination as first-line treatment of patients with metastatic her2/neu positive breast cancer.

phase ii non comparative study, assessing the safety (primarily cardiac safety) and efficacy in patients with locally advanced or metastatic her2/neu positive breast cancer not yet treated with chemotherapy for metastatic disease. myocet and taxotere will be given for a maximum of 6 cycles, herceptin treatment for 1 year is recommended. endpoints: cardiotoxicity (left ventricular ejection fraction decrease and/or symptoms of heart failure), serious other toxicity, disease progression.

Eligibility criteria:
inclusion criteria: * women with histologically documented metastatic or locally advanced metastatic her2/neu positive breast cancer at 1st line of palliative chemotherapy. * 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 ≤ 240 mg/m2 of doxorubicin or 450 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

Keywords: breast cancer metastatic cardiotoxicity liposomal doxorubicin trastuzumab docetaxel her2/neu positive metastatic breast cancer