Chemotherapy of a spontaneous mammary carcinoma in mice: relation between in vitro in vivo activity and blood and tumor concentrations of several antitumor drugs

A spontaneous mammary carcinoma growing in (C3H x 020)F ₁ mice was used for comparing the antitumor activity of 21 known drugs in vitro and in vivo. The tumor was cultivated in vitro in Rose chambers by utilizing the perforated cellophane strip technique, and the activity of the drugs added at different concentrations was evaluated according to morphologic criteria (lethality and cytotoxicity). The activity of the drug in vivo was established after intraperitoneal administration at various doses and schedules of treatment. There was agreement between the in vitro and the in vivo results in only seven of the 21 drugs tested. Blood and tumor concentrations for four selected drugs (6 mercaptopurine, daunorubicin, methotrexate, and hydroxyurea) were measured after single or repeated treatments. These data were helpful in interpreting the discrepancy between the observed activity of daunorubicin in vitro and its inactivity in vivo. In fact, the peak level of daunorubicin in the blood or in the tumor hardly reached the minimal concentration found effective in vitro. It is concluded that the prediction of in vivo effectiveness by in vitro activity may be improved by a better knowledge of the kinetics and metabolism of antitumor drugs.