Abstract
The effects of inralesional (il) versus intraperitoneal (ip) administration of cisplatin (12 mg/kg-24 mg/kg, single injection) were studied using transplantable squamous cell carcinoma of mice. The size of the tumor in the control and saline injected groups increased approximately 20 times and 70 times at 3 and 6 weeks, respetively, whereas tumor growth was inhibited by more than 50% in the cisplatin treated groups at 3 weeks. The inhibition was more pronounced in the il groups than in the ip groups at any stage of experiment. As compared to the ip group, relative tumor volumes in the it groups receiving 12 mg/kg and 18 mg/kg of cisplatin were less than 50% at 3 weeks.
Histologically, focal necrosis of the tumor tissue was seen only in the il groups from 1 day to 1 week at the dose of 12 mg/kg. Necrosis of individual tumor nest was also observed more frequently in this group than in the ip group, but in areas of residual tumor, swelling of nucleus, disapperrance of nucleolus, nuclear vacuolization, decrease of nuclear stainability and occurrence of giant, bizarre-shaped nuclei were almost equally seen in both groups. At the dose of 18 mg/kg there was no significant difference in these changes between the two groups. Althogh necrosis of individual tumor nest was seen in all animals with ip administration, focal necrosis of the tumor tissue was not encounterd any animal, whereas focal necrosis was seen in the 3 animals in the il group. Almost complete tumor necrosis was seen in 4 animals in the il group, and 1 animal in the ip group.
Mitotic index fell below O.5 in all cisplatin treated groups, but no statistical difference was noted between it and ip administration.
The flowcytometoric analysis of the nuclear DNA content showed a tendency to decreases in the S and G 2 M phase cell populations in the it group and increases in the ip group.
There were no differences in the weight loss and histological changes in the major organs between the two groups, but in contrast to 30% for the ip group, the rate of toxic death for the il group was 5% at 18 mg/kg. The results indicate that il administration may produce a bettter response of the tumor to cisplatin with less adverse effects than by systemic administration, possibly by maintaining higher levels of the agent in the tumor tissue.
