Effects of fluosol-DA and oxygen breathing on adriamycin antitumor activity and cardiac toxicity in mice

Tumor growth delays were obtained in the MX1 human breast carcinoma xenograft treated with various combinations of Adriamycin (doxorubicin), Fluosol-DA, and carbogen breathing (95% oxygen/5% carbon dioxide). Adding carbogen breathing (6 hours) or Fluosol-DA (Green Cross, Osaka, Japan) and air breathing to this drug treatment did not change the tumor growth delay observed. When 2 hours of carbogen breathing was delivered immediately after injection with Fluosol-DA and Adriamycin, a tumor growth delay of almost 36 days was observed, which was a significant increase from the tumor growth delay obtained with Adriamycin alone (P less than 0.01). Increasing the carbogen breathing time to 6 hours immediately after drug administration resulted in a tumor growth delay of about 43 days which was not statistically significantly different from the tumor growth delay seen with the complete treatment and 2 hours of carbogen breathing, but was different from the drug alone (P less than 0.005). A morphologic evaluation of Adriamycin cardiotoxicity in combination with Fluosol-DA and carbogen breathing was carried out. There was only mild cardiotoxicity in all treatment groups. There was a trend towards increased cardiotoxicity of Adriamycin as the treatment dose was increased from 1 to 4 mg/kg/dose, reaching statistical significance (P less than 0.05) for the Adriamycin (4 mg/kg/dose) + Fluosol-DA + carbogen breathing group when compared to the three treatment groups at 1 mg/kg/dose Adriamycin. The results of these studies indicate that there may be a therapeutic gain by the use of Fluosol-DA and carbogen breathing in combination with Adriamycin chemotherapy.