Cisplatin, as second-line therapy for metastatic breast cancer (MBC), has at best shown only modest response rates. At high doses, the toxicity profile of this drug may outweigh any potential benefits for MBC patients. We performed a phase II study to determine whether the investigational agent WR2721 would mitigate the toxicity of cisplatin in patients with MBC and to assess the antitumor response of cisplatin as salvage therapy. Thirteen women were enrolled in the study. Cisplatin was administered at a dose of 120 mg/m2 together with WR2721 at a dose of 910 mg/m2 intravenously every 21 days. Response was assessed at the end of two cycles, and toxicity was evaluated after each treatment cycle. No objective antitumor responses were noted. Three patients exhibited toxicity from cisplatin in the form of ototoxicity, nephrotoxicity, myelotoxicity, and persistent delayed nausea and vomiting necessitating discontinuation from the study. There was one death from renal failure. WR2721 itself caused significant but transient hypotension in 46% of the patients. In our experience, salvage chemotherapy with cisplatin in pretreated patients with MBC produced no objective responses. WR2721 did not prevent the occurrence of organ toxicity.