[Effect of the combination of cisplatin and peplomycin on Ehrlich ascites carcinoma and on head and neck squamous cell carcinoma transplanted to nude mice].

For the purpose of developing the optimal combination regimen with Cisplatin (CPDD) and Peplomycin (PEP), fundamental studies of the combination were made. In the experiment No. 1, Ehrlich ascites carcinoma, known to be sensitive to both cisplatin and peplomycin, was used as the experimental tumor. Six-week-old, male ICR mice, transplanted with this experimental carcinoma, were divided into 35 groups: the groups dosed with 8, 4 or 2mg/kg of cisplatinum, or 32, 16 or 8mg/kg of peplomycin alone, respectively, or in combination, with cisplatinum as the preceding medication or peplomycin as the preceding medication or both administered simultaneously, a control group, and an intact control group. Both drugs were administratered intraperitoneally by one-shot injection. The mean survival time and median survival time were used as parameters for the evaluation of drug effect. In the experiment No. 2, head and neck squamous cell carcinoma transplanted to nude mice was used as the experimental tumor. The doses of the drugs were the intermediate of those applied in the experiment No. 1; that is, cisplatin 4mg/kgr and peplomycin 16mg/kg. Both drugs were administered intraperitoneally by one-shot injection. The mice were divided into 4 groups: control group, a group receiving peplomycin alone, a group receiving cisplatin alone and a group receiving the combination of the two drugs. The antitumor effects of the drugs were evaluated by the changes in the volume of the tumor in each group. The results indicated following conclusions. 1. In the experiment No. 1, the combination of CPDD and PEP proved to exert a synergistic effect on more than half of the so treated groups. The administration of CPDD as the preceding medication was found to be more effective but less toxic than the other two administration sequence, and its difference from the findings in the group treated with PEP as the preceding medication was of statistical significances.2. In the experiment No. 2, the antitumor effects were highest in the group of combination treatment, and it was confirmed by the statistical analysis that the synergistic effects were obtained by the combined administration of both drugs. 3. The mechanism of the observed synergism in these combined administration was discussed from following three viewpoints: pharmacodynamic, cell kinetic and DNA repair; and the last seemed to be of the most probable mechanism. 4. From the findings in these preclinical studies and the mechanism of the synergism, the administration of CPDD as the preceding medication seemed to be the desirable medication sequence.