1982 Volume 73 Issue 11 Pages 1375-1394
Six human genitourinary tumor xenografts sustained by serial transplantation in nude mice were tested for sensitivity to anticancer agents in our laboratory. A renal cell carcinoma xenograft (NM-R-1) was treated intraperitoneally with some anticancer agents and the effects were evaluated according to tumor volume (growth curve of tumor, T/C ratio on day 43 after tumor implantation) and histology.
NM-R-1 was mainly composed of clear cells, and its histologic features were preserved even afrer serial transplantations. NM-R-1 used during this study was in its 7th to 10th passage through the nude mice. Successful transplantation rate was close to 100% by using these passages and the tumors maintained a constant growth rate.
Platinum compounds (cis platinum diaminodichloride (CDDP), platinum D-glucuronate diaminocylohexane trans-d-dach (d-GHP)) were injected on days 1, 5, and 9. CDDP, 5.0mg/kg/inj, 2.5mg/kg/inj and d-GHP, 50mg/kg/inj, 25mg/kg/inj were effective. T/C ratios of each treated group were 10.8%, 19.5%, 8.5% and 9.7%. Histologically, d-GHP was more effective than CDDP, but the drug toxicity (weight loss of treated mice) of both drugs were severe.
Ifosfamide (IFM) was injected daily for 5 days in one treated group and, in another group, it was injected daily for 5 days following once a week. In both groups, the most effective dose was 100mg/mg/inj. In the latter group, the T/C ratio was only 2.2%, and weight loss of the mice was not severe. The degree of histologic change was parallel to the dosage employed.
Vinblastin was injected once a week for 5 weeks, but it was less effective than IFM or the platinumm compound for NM-R-1.
NM-R-1 was also treated with CDDP combined with IFM. When combined, the dosages of CDDP were 5.0, 2.5, and 1.25mg/kg/inj, and the dosages of IFM were 100, 50, and 25mg/kg/inj. Injection intervals of each drug were the same as in single agent treatment. Growth inhibitory effects were seen in all treated groups. This was especially true with CDDP treatments of 5.0mg/kg/inj and IFM, 50mg/kg/inj, the tumor size reduced markedly and 3 of 5 tumors disappeared macroscopically. These results indicate some sort of synergism between CDDP and IFM. Mean body weight of treated mice decreased about 30% compared to that of the controls.
Tissue concentrations of IFM and its metabolites were investigated in nude mice after an injection dose of 100mg/kg intraperitoneally. IFM concentration in the tumor was lower than the blood level when injected on Day 70. It did not change when injected on Day 35. IFM was at its highest concentration in the kidney, and that level was higher than blood level in the liver and the lung.
