Terwogt J M, Mandjes I A, Sindermann H, Beijnen J H, ten Bokkel Huinink W W
Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam.
Br J Cancer. 1999 Mar;79(7-8):1158-61. doi: 10.1038/sj.bjc.6690184.
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 of 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 phase II study was performed to determine the efficacy and tolerability of topically applied miltefosine in patients with cutaneous metastases from breast cancer. Thirty-three patients in total entered the trial. A 6% miltefosine solution was applied once daily in the first week and twice daily in the following weeks. The planned minimum treatment duration was 8 weeks. We found an overall response rate of 43% for 30 evaluable patients, composed of 23% complete response and 20% partial response. The median response duration was 18 weeks, range 8-68. Toxicity consisted mainly of localized skin reactions, which could be controlled by a paraffin-based skin cream and, where 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.
乳腺癌的皮肤转移灶可能带来严重的治疗难题，尤其是对传统治疗产生耐药时。局部应用细胞毒性药物可能是一种颇具吸引力的新治疗方式，且无明显全身毒性。选择米替福新是因其在乳腺癌模型中的疗效。将不同链长的烷基化甘油与水的混合物用作药物载体，以溶解米替福新并进一步促进其透皮吸收。在我们研究所进行了一项II期研究，以确定局部应用米替福新对乳腺癌皮肤转移患者的疗效和耐受性。共有33例患者进入试验。第1周每天应用1次6%米替福新溶液，之后几周每天应用2次。计划的最短治疗疗程为8周。对于30例可评估患者，我们发现总体缓解率为43%，其中完全缓解率为23%，部分缓解率为20%。中位缓解持续时间为18周，范围为8 - 68周。毒性主要表现为局部皮肤反应，可通过石蜡基护肤霜控制，必要时调整剂量。未观察到全身毒性。我们得出结论，局部应用米替福新是乳腺癌皮肤转移患者的一种有效治疗方式。
