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.