A new concentrated perfluorochemical emulsion and carbogen breathing as an adjuvant to treatment with antitumor alkylating agents.
Many anticancer drugs require oxygen to be cytotoxic or are selectively cytotoxic toward cells under oxygenated conditions. The effects of the dilute perfluorochemical emuolsion Fluosol with a wide variety of chemotherapeutic agents have been explored; however, it has not been possible to determine the optimal level of circulating perfluorochemical emulsion with anticancer drugs because the volume of Fluosol that may be administered is limiting. Using a new concentrated perfluorochemical emulsion, a wide range of perfluorochemical doses has been examined in combination with melphalan, cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in the FSaIIC fibrosarcoma. When the perfluorochemical emulsion was administered by injection i.v. just prior to the injection of melphalan (10 mg/kg), cyclophosphamide (150 mg/kg) or BCNU (50 mg/kg), the greatest tumor growth delays were obtained with dosage levels between 4 g and 12 g of the perfluorochemical perfluorooctyl bromide/kg. With each drug the greatest tumor growth delays were obtained when the drug was prepared in the emulsion and the combination injected i.v. In each case, each dose of drug was followed by 6 h of breathing carbogen. The addition of the perfluorochemical emulsion/carbogen breathing to treatment with melphalan, BCNU or cyclophosphamide resulted in significant increases in the killing of tumor cells by these drugs without a concomitant increase in toxicity to bone marrow granulocyte/macrophage-colony-forming units. In each case, preparing the drug in the perfluorochemical emulsion was most effective. These results indicate that clinical trial of this perfluorochemical emulsion/carbogen breathing in combination with cancer chemotherapy may be warranted.
Teicher
B A
BA
Dana-Farber Cancer Institute, Boston, MA 02115.
Holden
S A
SA
Ara
G
G
Ha
C S
CS
Herman
T S
TS
Northey
D
D
D000280:Administration, Inhalation; D000477:Alkylating Agents / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000009:adverse effects; D002330:Carmustine / Q000008:administration & dosage; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004655:Emulsions; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006842:Hydrocarbons, Brominated; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000008:administration & dosage* / Q000009:adverse effects; D014407:Tumor Cells, Cultured
D000477:Alkylating Agents; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D002245:Carbon Dioxide; C011700:carbogen; D003520:Cyclophosphamide; C003072:perflubron; D008558:Melphalan; D010100:Oxygen; D002330:Carmustine