title: Effect of a bovine hemoglobin preparation on the response of the FSaIIC fibrosarcoma to chemotherapeutic alkylating agents.
abstract: Polymerized bovine hemoglobin solutions (PBHS) are being actively investigated as blood substitutes. In studies analogous to those we conducted with perfluorochemical emulsions/carbogen, we have examined the effect of PBHS +/- carbogen (95% O2, 5% CO2) breathing on the antitumor efficacy of melphalan, cyclophosphamide, N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) and cis-diamminedichloroplatinum(II) (cis-platin). The tumor growth delay of the FSaIIC fibrosarcoma treated with melphalan (10 mg/kg), cyclophosphamide (150 mg/kg), cisplatin (10 mg/kg) and BCNU (15 mg/kg) was increased about 2.2-fold, about 2.1-fold, about 1.2-fold and about 1.5-fold, respectively, when PBHS (12 mg/kg) was administered i.v. before each drug was injected i.p. The tumor growth delay produced by each drug was further increased when carbogen breathing for 6 h was allowed after administration of the drug and PBHS. In tumor cell survival experiments 24 h following drug treatment, the addition of PBHS increased the tumor cell killing of both melphalan and cyclophosphamide by about a factor of 10 at the lowest doses of each drug tested (10 mg/kg for melphalan and 100 mg/kg for cyclophosphamide) compared to the drug alone. However, at higher drug doses this effect was lost. The toxicity of each antitumor agent toward bone marrow (granulocyte/macrophage-colony-forming units) was increased 2- to 3-fold by the combined treatment. These results suggest that use of PBHS +/- carbogen breathing may add significantly to the efficacy of antitumor alkylating agents, however, the in vivo/in vitro data suggest that there will be increased bone marrow toxicity with this approach. This needs to be taken into account in the design of clinical trials.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: B A
authors.initials: BA
authors.lastname: Teicher
authors.forename: T S
authors.initials: TS
authors.lastname: Herman
authors.forename: R E
authors.initials: RE
authors.lastname: Hopkins
authors.forename: K
authors.initials: K
authors.lastname: Menon
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology; D002417:Cattle; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004357:Drug Synergism; D005354:Fibrosarcoma / Q000188:drug therapy*; D006454:Hemoglobins / Q000008:administration & dosage*; D008297:Male; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000477:Alkylating Agents; D006454:Hemoglobins; D002245:Carbon Dioxide; C011700:carbogen; D003520:Cyclophosphamide; D002945:Cisplatin; D008558:Melphalan; D010100:Oxygen; D002330:Carmustine