Oral VRL offers easier administration, better quality of life, and cost saving. This study aimed to evaluate the treatment efficacy in terms of tumor response of the two formulations of vinorelbine (VRL, oral and IV) in combination with epirubicin (EPI); and the effect of EPI co-administration on VRL pharmacokinetics (PK) in Chinese patients with metastatic breast cancer (MBC) using a phase 2, open label, randomized trial. Patients were aged 18-70 years, had histologically confirmed MBC, Karnofsky Performance Status >= 70%, and life expectancy >= 12 weeks. The treatment consisted of 6 cycles of 3 weeks each. VRL dose was: (Oral-VRL) 60 mg/m(2) for cycle 1, 80 mg/m(2) for cycles 2-6, and (IV-VRL) 25 mg/m(2) for cycle 1 and 30 mg/m(2) for cycles 2-6. EPI dose of 75 mg/m(2) was given on day 1 in both arms for all cycles. 133 patients were enrolled: 66 in Oral-VRL and 67 in IV-VRL arms. The median age for Oral-VRL and IV-VRL arms was 48.4 and 50.0 years, respectively. Objective response rates were 50.0% (95% CI 37.4-62.6%) for Oral-VRL and 53.7% (95% CI 41.1-66.0%) for IV-VRL. Both treatment arms met the efficacy objective target of at least 31 responses, demonstrating efficacy as first-line treatment for MBC. Similar blood PK profiles, exposures, and VRL clearance were observed between VRL+EPI vs VRL-only modalities for both arms. Oral VRL is comparable to IV VRL and an effective first-line treatment for Chinese patients with MBC. The activity of VRL+EPI combination is unaltered when VRL is given orally at recommended doses.