|Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Background : Intraarterial neoadjuvant chemotherapy with Pirarubicin(THP), Cisplatin (CDDP) and Peplomycin (PEP) (TPP therapy) showed a high primary effect on oral cancers (Hashimoto et al,1993). Mori et al reported that 5 year survival rate of stage IV after TPP therapy were 73.3% in group of intraarterial infusion, and 43.6 % in group of venous infusion, respectively. Experimentally, intraarterially preadministered THP showed a beneficial effect on CDDP con- centrations in the tissue of the lymph nodes. After 5HT receptor antagonists such as granisetron (GRN) became available for clinical use, the clinical response to TPP therapy became lower (Komatsu et al, 1997). In this paper, the influences of antiemetics on the transition of CDDP into tissues was studied. Materials & Methods : VX-2 carcinoma was transplanted to the dorsum pedis of Japanese white rabbits (average body weight 3.0 kg). The tumor was treated intraarterially with CDDP (2mg/kg) via the femoral artery after administrat
ion of THP 1mg/kg(bolus) via the femoral artery. In experimental groups, GRN (1mg/kg), Azasetron(AZA) (3mg/kg), Ondansetron(OND) (1mg/kg) or Metoclopramide(MCP) (3mg/kg) were administered intravenously via the auricular vein 30 minutes before administration of CDDP, and saline was administered in the control group. The tissue, including the tumor and the popliteal lymph node on the same side, were collected along with the blood 30 minutes after the administration of CDDP.
Results : The concentrations of CDDP in the lymph nodes was observed to be significantly higher in the control group (3.39^^+__-3.96 μ g/g) than in the GRN group (1.81^^+__-0.08 μ g/g). From additional experiments, the CDDP levels in lymph nodes were 2.31^^+__-11.50 μ g/g (n=4) in the control group, 2.22^^+__-0.79 μ g/g in the AZA group (n=4), 1.90^^+__-0.43 μ g/g in the OND group (n=4) and 3.39^^+__-5.43 μ g/g in the MCP group (n=4), respectively. There were no significant differences in the CDDP levels in the lymph nodes among the groups. The CDDP levels in the tumors of each groups did not show no specific tendencies. These results were supported by the histological findings that poor vascularlization was observed.
Conclusion: It was indicated experimentally that GRN decreases the level of CDDP in the lymph nodes significantly as comparied with the control group. However, it was clarified experimentally that AZA, OND and MCP do not decrease CDDP levels of in the lymph nodes, as compeared with the control group. Less