Summary
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) andcis-diamminedichloroplatinum(II) (cisplatin). 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.
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Abbreviations
- PBHS:
-
polymerized bovine hemoglobin solution
- BCNU:
-
N,N′-bis(2-chloroethyl)-N-nitrosourea
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This work was supported by NIH grant PO1-19589 and a gift from Biopure Inc., Boston, Mass.
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Teicher, B.A., Herman, T.S., Hopkins, R.E. et al. Effect of a bovine hemoglobin preparation on the response of the FSaIIC fibrosarcoma to chemotherapeutic alkylating agents. J Cancer Res Clin Oncol 118, 123–128 (1992). https://doi.org/10.1007/BF01187500
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DOI: https://doi.org/10.1007/BF01187500