制吐剤の動注化学療法に及ぼす影響に関する基礎的研究

背景：动脉内新辅助化疗吡柔比星（THP）、顺铂（CDDP）、培霉素（PEP） （TPP治疗）对口腔癌有很高的原发性疗效（Hashimoto et al .,1993）。Mori等报道，动脉输注组TPP治疗后IV期5年生存率为73.3%，静脉输注组为43.6%。实验表明，动脉内预先给药THP对淋巴结组织中CDDP浓度有有益的影响。在5HT受体拮抗剂如格拉司琼（granisetron， GRN）可用于临床后，对TPP治疗的临床反应变得较低（Komatsu et al, 1997）。本文研究了止吐药对CDDP向组织转移的影响。材料与方法：将VX-2癌移植至平均体重3.0 kg的日本大白兔足背。经股动脉给药后，经股动脉给药CDDP (2mg/kg)；经股动脉给药THP （1mg/kg）。实验组在给药前30 min经耳静脉给予GRN （1mg/kg）、阿扎司琼（AZA） （3mg/kg）、昂丹司琼（OND） （1mg/kg）或甲氧氯普胺（MCP） （3mg/kg），对照组给予生理盐水。CDDP给药30分钟后，取肿瘤及同侧腘窝淋巴结组织与血。结果：对照组淋巴结CDDP浓度（3.39^^+_ ~ 3.96 μ g/g）明显高于GRN组（1.81^^+_ ~ 0.08 μ g/g）。在其他实验中，对照组淋巴结CDDP水平为2.31^^+_ -11.50 μ g/g (n=4)， AZA组为2.22^^+_ -0.79 μ g/g (n=4)， OND组为1.90^^+_ -0.43 μ g/g (n=4)， MCP组为3.39^^+_ -5.43 μ g/g （n=4）。各组淋巴结CDDP水平差异无统计学意义。各组肿瘤中CDDP水平无明显变化趋势。这些结果得到了组织学结果的支持，即观察到血管化不良。结论：实验表明，与对照组相比，GRN可显著降低淋巴结内CDDP水平。然而，实验表明，与对照组相比，AZA、OND和MCP并没有降低淋巴结中CDDP的水平。少

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 … More 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