title: Effects of Fluosol-DA and oxygen breathing on adriamycin antitumor activity and cardiac toxicity in mice.
abstract: 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.
authors: Dana-Farber Cancer Institute, Boston, MA 02115.
authors: B A
authors: BA
authors: Teicher
authors: S A
authors: SA
authors: Holden
authors: J M
authors: JM
authors: Crawford
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005466:Fluorocarbons / Q000008:administration & dosage*; D006331:Heart Diseases / Q000139:chemically induced*; D006895:Hydroxyethyl Starch Derivatives; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000008:administration & dosage*; D014183:Transplantation, Heterologous
chemical_list: D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D004317:Doxorubicin; D010100:Oxygen