Experimental study on the effect of pre-administered THP-ADM on the tissue levels of CDDP.

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INTRODUCTION : In our clinical study, neoadjuvant chemoterapy of THP-ADM,CDDP and PEP (TPP therapy) showed high primary effect on head and neck cancer. The roles of pre-admisintered THP-ADM in TPP therapy has not been investigated thoroughly enough. In this paper, the effects of pre-administered THP-ADM on the tissue levels of CDDP were studied experimentally.MATERIALS & METHODS : VX-2 carcinoma transplanted into the leg of Japanese white rabbits was treated intraarterially or intravenously with CDDP 0.5 hrs (group IA-0.5 or IV-0.5), 24 hrs (group IA-24 or IV-24) and 48 hrs (group IA-48 or IV-48) after administrating THP-ADM,or only CDDP without THP-ADM (group C). The dose of THP-ADM was 1 mg/kg, and CDDP 2 mg/kg, respectively. Blood and tissue were collected 30 minutes after the administration of CDDP.The level of CDDP was measured by the FAAS,and THP-ADM and their metabolites were analyzed by the HPLC.RESULTS : The CDDP level (0.815(]SY.+-。[)0.199mug/g) in the tumors in group IA-0.5 … More was significantly lower than in group C (2.898(]SY.+-。[)1.213mug/g). There was no marked difference in the CDDP levels observed in the tumors among group IA-24 (1.533(]SY.+-。[)1.973mug/g), group IA-48 (1.425(]SY.+-。[)1.243mug/g) or group C.The level of CDDP in the lymph node was observed to be significantly higher (p<0.05) in group IA-24 (3.391(]SY.+-。[)1.991mug/g) than in group IA-0.5 (1.357(]SY.+-。[)0.427mug/g), group IA-48 (2.903(]SY.+-。[)1.182mug/g) or group C (1.195(]SY.+-。[)0.818mug/g). There were no significant differences in the plasma CDDP levels among the four groups. Similarly, there were no significant differences in the CDDP levels among group IV-0.5, IV-24 and IV-48.DISCUSSION : Experimentally, pre-administered THP-ADM demonstrated the beneficial effects on CDDP consentration in the tissue. Potentially, this effect may explain the clinical evidence for TPP therapy. These effects of combined chemotherapy of THP-ADM and CDDP is suspected to be one type of the biochemical modulations. Therefore, these findings tentatively support the theory of TPP therapy that is an adequate treatment of the head and neck cancer. Less