Preliminary results of a phase II study of liposomal cisplatin-vinorelbine combination as first-line treatment in HER2/neu negative metastatic breast cancer (MBC)

Abstract

1068 Background: The frequent use of anthracyclines and taxanes in breast cancer's adjuvant setting has lead to drug resistance and cardiac toxicity. This has raised the need for new agents in the metastatic setting. Cisplatin-vinorelbine combination recently showed interesting results with an overall response rate of 64%. Nevertheless, the use of cisplatin was limited by the frequently induced nausea, vomiting, and nephrotoxicity. Liposomal cisplatin (Lipoplatin) is a nontoxic alternative agent to cisplatin. The aim of this study is to evaluate the efficacy and safety of liposomal cisplatin-vinorelbine combination in first line MBC patients (pts). Methods: From August 2007 to October 2008, 30 of 35 programmed pts with MBC and no prior treatment for their metastatic disease, PS 0–2, HER2/neu negative, and at least one measurable lesion, were enrolled. Of these 30 recruited pts, 26 with available data were analyzed. Treatment included I.V. vinorelbine 30 mg/m2 on days 1 and 8, and liposomal cisplatin 120 mg/m2 on days 1, 8, and 15. Cycles were repeated every 3 weeks for a total of 6 cycles. Primary objectives: objective response rate, time to treatment failure (TTF), and time to progression (TTP). Secondary objectives: overall survival and treatment-related toxicity. Results: The median age was 49 years (29–74). 69% of pts had visceral metastases. 35% had one metastatic site, 46% had 2, 19% had 3 or more. A total of 120 cycles were administered with a median number of 6 per patient. At the time of the analysis 22 pts were evaluable for response. An objective tumor response was observed in 11 pts (50%) and complete response in 1 patient (4.5%). Ten (45.5%) pts had stable disease. The median TTF and TTP were 5 and 8 months respectively. All pts (26) were evaluable for toxicity. The majority of adverse events were mild to moderate. No WHO grade 3–4 nephrotoxicity or neuropathy was noted. Grade 3–4 nausea/vomiting was observed in 3 pts (11.5%). Three pts (11.5%) had grade 3 anemia and 18 pts (69.2%) had grade 3–4 neutropenia. Three pts (11.5%) developed febrile neutropenia with no secondary mortality. Conclusions: The new combination of liposomal cisplatin and vinorelbine shows promising activity and good tolerance as first line treatment for HER2/neu negative MBC. Pts’ enrollment is ongoing. Updated results will be presented at the meeting. [Table: see text]