Phase II trial of topically applied miltefosine solution in patients with skin-metastasized breast cancer

Skin deposits from breast cancer can present serious therapeutic problems, especially when resistant to conventional therapy. Topical application of a cytotoxic drug may represent an attractive new treatment modality devoid o f major systemic toxicity Miltefosine was selected because of its efficacy in breast cancer models. A mixture of alkylated glycerols of various chain lengths and water was used as the pharmaceutical vehicle to dissolve and to further facilitate tissue penetration of miltefosine. In our Institute a p hase II study was performed to determine the efficacy and tolerability of t opically applied miltefosine in patients with cutaneous metastases from bre ast cancer. Thirty-three patients in total entered the trial. A 6% miltefos ine solution was applied once daily in the first week and twice daily in th e following weeks. The planned minimum treatment duration was 8 weeks. We f ound an overall response rate of 43% for 30 evaluable patients, composed of 23% complete response and 20% partial response. The median response durati on was 18 weeks, range 8-68. Toxicity consisted mainly of localized skin re actions, which could be controlled by a paraffin-based skin cream and, wher e appropriate, by dose modification. No systemic toxicities were observed. We conclude that topical miltefosine is an effective treatment modality in patients with skin metastases from breast cancer.