A pharmacological rationale for neoadjuvant chemotherapy with adriamycin in locally advanced breast cancer.

: Some locally advanced neoplastic diseases (i.e. head and neck cancer, breast cancer and osteogenic sarcoma), benefit from neoadjuvant chemotherapy with a resultant enhanced operability and a longer disease-free survival. The pharmacological study of the tissue distribution of adriamycin in patients affected by locally advanced breast cancer has shown a preferable tropism of the drug toward the primary tumor and axillary lymph nodes. Median concentrations of the drug in the tumor were: 9.68 micrograms/gr at 30 minutes, 8.71 micrograms/gr at 24 hours and 6.44 micrograms/gr at 48 hours. Median concentration in lymph nodes at 48 hours was 10.80 in normal and 16.62 in metastatic. Lower concentrations were found at 48 hours in the mammary gland (mean 1.72 micrograms/gr), skin (mean 0.59 micrograms/gr) and in muscle tissue (mean 1.83 micrograms/gr in normal and 2.41 micrograms/gr in metastatic). As regards acute toxicity, we observed that grade II-III leukopenia was associated with longer plasmatic T1/2 beta (3 out of 6 patients) and that grade II mucositis was related to high plasma AUC values (3 out of 6 patients). Nausea and vomiting and alopecia seem to be unrelated to plasma pharmacokinetics parameters. After a median follow-up of 36 months it is suggestive that high drug concentrations in carcinoma and in metastatic lymph nodes may be predictive of longer disease-free survival and overall survival. These data give a further rationale for the use of polychemotherapies containing adriamycin in the pre-operative treatment of locally advanced breast cancer.