CDDP腎毒性に対するFosfomycinの予防効果の検討

Abstract

24症例の泌尿器科癌を対象にCisplatin (CDDP)投与を61コースに施行, このうち39コースにFOMを添加し, CDDP腎毒性軽減効果を検討した.1)尿中NAG活性, FENaはCDDPによる急性腎毒性の指標として有用であるが, Ccrは不適と思われた.2) 1日投与群(CAP療法:CDDP 60～70 mg/m2×1日)ではFOMの腎毒性軽減効果は明らかではなかった.3) 5日投与群(CDDP療法, PVB療法:CDDP 20 mg/m2×5日)ではFOMの有意な腎毒性軽減効果がみられた.4)投与前CcrはCDDP腎毒性の発現を強く左右し, Ccrが低いほど尿中NAG活性は高値を示すが, Ccrが投与前50 ml/min以上あればFOM添加にて有意な腎毒性軽減効果を認めregimenどおりのCDDP投与が可能であると思われた

From 1985 to 1986, cisplatin (CDDP) therapy was performed 61 times in 24 patients with urological cancer. Thirty nine courses used fosfomycin (FOM) 4 g/day from the day before CDDP administration to the last dose of CDDP, and we statistically evaluated the prophylactic effect of FOM on CDDP nephrotoxicity using urinary NAG and FENa as parameters (t-test). In the 1-day CDDP group (CDDP 60-70 mg/m2 x 1 day) with FOM a peak NAG was seen on the 1st day but no significant NAG change, FENa has a peak on the 1st day, no significant increase between the previous and the 1st day, but a significant decrease was seen between the 3rd and the 5th day (p less than 0.05). In the 5-day CDDP group (CDDP 20 mg/m2 x 5 day) NAG reached a peak level on the 5th day with FOM, showed significant increase (p less than 0.05; between the previous and the 5th day) and decrease (p less than 0.01; between the 6th and the 14th), compared to those without FOM. FENa change tended to be similar, showing a significant increase, (p less than 0.05; between the 2nd and 4th) and decrease (p less than 0.05; between the 4th and 7th) with FOM but no significant change without FOM. NAG changes with FOM were classified by pre-CDDP dose creatinine clearance (Ccr, ml/min) into 3 groups (under 50, 50-100, over 100). In the 1-day CDDP group with any Ccr no significant NAG change obtained, but, in the 5-day CDDP group with 50-100 Ccr seen a NAG peak on the 6th day, significant increase (p less than 0.05; between the previous and the 6th) and decrease (p less than 0.05; between 6th and 12th). With over 100 Ccr NAG has 4th day peak, significant increase (p less than 0.05; between the previous and the 4th), and decrease (p less than 0.05; between 4th and 8th). A prophylactic effect of FOM on CDDP nephrotoxicity was found in the 5-day CDDP group not in the 1-day CDDP group, using urinary NAG and FENa. PVB and single CDDP regimen (5 day CDDP group) with FOM can be performed safely, if the pre-CDDP dose Ccr is over 50.