Phase II study of miltefosine 6% solution as topical treatment of skin metastases in breast cancer patients

Topical treatment of skin metastases with a cytotoxic agent is attractive f or its easy self-administration and absence of major systemic interference. Miltefosine exerts its cytotoxicity by acting on cell membrane phospholipi ds and can he administered topically. Twenty breast cancer patients with pr ogression of skin metastases were treated with a 6% solution of miltefosine , which was topically administered once daily during the first week and twi ce daily thereafter. Sixteen out of 20 patients also had metastatic disease at other sites. Concomitant systemic treatment when ongoing for at least 2 months prior to study entry was permitted, and consisted of chemotherapy a nd hormonal therapy in seven and nine patients, respectively. Prior palliat ive cytotoxic and hormonal therapy had been administered to 11 and 19 patie nts, respectively. No grade 3 and 4 toxicity occurred. Miltefosine therapy was discontinued in two patients due to nausea and in one patient due to sk in toxicity. Grade 1 and 2 adverse skin reactions, and nausea and vomiting were seen in 11 and two patients, respectively. In 18 patients evaluable fo r response, four partial responses were noted (response rate 22%), while se ven patients had stable disease. Three partial responses were observed in p atients in whom the skin lesions were smaller than 1.5 cm(2). Median durati on of respons was 2.5 months and median time to progression for all patient s was 1.9 months. In this study topically applied miltefosine for metastati c skin lesions of breast cancer showed modest activity in a relatively heav ily pretreated patient population, without serious systemic toxicity. [(C) 2000 Lippincott Williams & Wilkins.].