Experimental study on the effect of large-dose intratumoral OK-432 administration in mice

This experimental study was undertaken to evaluate the effectiveness of a large-dose intratumoral administration of OK-432, which has already been found to be effective when combined with Mitomycin-C, 5-fluorouracil, and cytosine arabinoside, and/or small-dose of OK-432 in clinical use. Large-dose of OK-432 was administered intratumorally 15 days after the subcutaneous inoculation of 2.5 X 10(6) Ehrlich carcinoma cells. At the same time, 2.5 X 10(6) tumor cells were re-challenged intraperitoneally. A combined treatment with a small-dose of OK-432 and Mitomycin-C, cyclophosphamide, or 5-fluorouracil was also made. As a large-dose of OK-432, three-dose regimen of 1,000, 500, and 100 KE/kg was tested. As a small-dose of OK-432, 4 consecutive daily intramuscular injection of 50 KE/kg was examined. From the results obtained the initial intratumoral administration of a large-dose of OK=432 was found to be beneficial for the following combined treatment with a small-dose of OK-432 and Mitomycin-C or cyclophosphamide. The change of phytohemagglutinin (PHA) responsiveness of spleen cells after intratumoral injection of a large-dose of OK-432 was investigated in mice. These results indicated a decrease of PHA responsiveness of spleen cells according to the tumor growth. The intratumoral large-dose administration of OK-432 suggested inhibition of the decrease in PHA responsiveness. The most effective and suitable dose in this experiment was found to be 500 KE/kg in the three-dose regimen.