The Efficacy and Safety of Pegylated Liposomal Doxorubicin Compared With Capecitabine as First Line Chemotherapy for Metastatic Breast Cancer (P04445/MK-2746-071)

Inclusion Criteria

• Patients must be female.
• Patients must have metastatic disease of a cytological or histological confirmed breast cancer.
• Patients must be 18 years or older.
• Patients should have evaluable disease (at least uni-dimensionally measurable lesion according to the RECIST criteria in at least one site that has not been irradiated), however, patients who only have non-measurable/evaluable disease are not excluded. Also patients with only bone metastasis are not excluded.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) 0-2.
• Patients must have a sufficient life expectancy to be treated with chemotherapy.
• Patients must be willing and able to complete study questionnaires.
• Patients must have adequate renal function as evidenced by serum creatinine =45 mL/min (if serum creatinine is > 1.5 mg/dL but =9.0 g/dL, and platelet count >=100x10^9/L.
• Patients must have adequate liver function as evidenced by bilirubin of <=1.5 times the upper limits of normal (ULN) and alkaline phosphatase <=3 times, ULN unless related to liver metastasis.
• Patients must have Sodium and Potassium values within normal limits.
• Patients whose clinical condition (co-morbidity) allows a treatment with monotherapy or who expressed their wish to be treated with monotherapy.
• Patients must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria

• History of receiving prior chemotherapy in the metastatic setting (Note: patients may have had

hormonal therapy or chemotherapy in the adjuvant setting; patients may have received hormonal therapy in metastatic setting, patients may have received local radiotherapy).

• Patients with positive estrogen- / progesterone-receptor status, where an endocrine therapy is indicated. However, patients progressing under hormonal therapy are not excluded.
• Patients with known hypersensitivity to doxorubicinhydrochlorid or to any of the excipients OR known hypersensitivity to capecitabine or fluorouracil or to any of the excipients.
• Patients with known DPD (dihydro pyrimidine dehydrogenase) deficiency.
• Patients who are receiving a concomitant treatment with sorivudine or its chemically related analogues, such as brivudine.
• Patients who are taking concomitant medications (except bisphosphonates) for metastatic disease, including hormonal therapy, radiation therapy, trastuzumab, or biologicals are also not permitted.
• Patients with Human epidermal growth factor receptor 2 (Her-2/neu) overexpressing tumors with the most recent evaluation as the relevant result
• immunologically Her2neu 3+ positive
• Her2neu-2+ positive and ´Fluorescent in-situ hybridization (FISH)´ positive
• History of treatment with capecitabine
• History of treatment with anthracyclines in the adjuvant setting exceeding cumulative doses of anthracyclines by more than 360 mg/m^2 doxorubicin (or equivalents, i.e. 600mg/m^2 epirubicine).
• Patients with anthracycline resistant disease are not permitted. Anthracycline resistance is defined as development of locally recurrent or metastatic disease while on adjuvant anthracycline therapy, or relapse less than 12 months after completion of anthracycline therapy.
• Strong remission pressure that requires polychemotherapy with the exception of patients who are not suitable for a treatment with polychemotherapy or not accepting polychemotherapy.
• Evidence of primary or metastatic malignancy involving the central nervous system unless previously treated and asymptomatic for 3 months or greater.
• Patients with reduced liver functions (evidenced by bilirubin of above 1.5 times the upper limits of normal (ULN); alkaline phosphatase above 3 times ULN (except related to liver metastasis, in which case <=5 x ULN).
• Dyspnea on exertion.
• History of cardiac disease, with New York Heart Association Class II or greater, or clinical evidence