Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes

BACKGROUND. Stealth liposomes hold promise as a mode of delivering cytotoxi c agents selectively to tumors in cancer patients. The objective of this st udy was to determine whether stealth liposomal doxorubicin accumulates sele ctively in bone metastases based on clinical material obtained from two pat ients with breast carcinoma. METHODS. Tumor tissue was obtained from two women (ages 33 years and 41 yea rs, respectively) with metastatic breast carcinoma who responded to treatme nt with stealth liposomal doxorubicin and later underwent a surgical fixati on procedure to treat a pathologic fracture of the femur. Drug levels in th e tumor and adjacent muscle were examined by high performance liquid chroma tography analysis in both patients and by fluorescence microscopy in one of the patients. RESULTS. Bone tumor fragments obtained during surgery performed 6 days afte r the administration of the 12th course of stealth liposomal doxorubicin in 1 patient and 12 days after the administration of the 16th course of steal th liposomal doxorubicin in the second patient had a 10-fold greater concen tration of liposomal doxorubicin than tumor free muscle. Doxorubicin fluore scence and specific nuclear staining showed good colocalization, thus confi rming the presence of the liposome-delivered drug in the nuclei of tumor ce lls. CONCLUSIONS, Using skeletal muscle as a comparator, stealth liposomal doxor ubicin accumulates selectively in metastatic breast carcinoma cells within bone. Cancer 1999;86:72-8. (C) 1999 American Cancer Society.