THE INFLUENCE OF PLATINUM DRUGS ON THE RADIATION RESPONSE OF RAT KIDNEYS

The influence of a single bolus injection of platinum drugs on the rad iation sensitivity of the kidneys was investigated in WAG/Rij rats. Dr ugs employed were cis-diammine-dichloroplatinum(II) (cisplatin, CDDP), cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) (carboplatin, CBDCA) and cis-dichloro, trans-dihydroxybis-isopropylamine platinum(Iv ) (iproplatin, CHIP), Both kidneys were irradiated with a range of sin gle X-ray doses while drugs were administered at 1 day or 1 week befor e irradiation. Maximum tolerated drug doses (defined as the LD(1), the dose resulting in a mortality of 1%) were given. Damage inflicted upo n the kidneys was monitored by determination of several parameters ind icative of kidney function. Isoeffective radiation doses were calculat ed from these data for each treatment group at 4-8-week intervals up t o 80 weeks following treatment. At each assay time, dose modifying fac tors (DMF) were calculated for each drug/radiation combination. The me an DMFs were highest for CDDP: approximately 1.6. Those for CBDCA and CHIP were lower: approximately 1.1 and 1.2, respectively. The CHIP DMF s were significantly different from unity. When the radiation was give n in 4 or 8 daily fractions (4 fractions/week) the DMFs for CDDP were identical to those obtained with single doses. For CBDCA and CHIP, how ever, the DMFs after fractionated treatments were not significantly di fferent from unity. Analysis in terms of the linear-quadratic (LQ) mod el indicated that not one of the three; drugs had an effect on the alp ha/beta ratio, and hence on the fractionation sensitivity of the rat k idney. Consequently, if these data are extrapolated to the clinical se tting, the administration of these drugs at the maximum tolerated dose preceding a fractionated radiation treatment should not be expected t o result in extra, unexpected, radiation toxicity of the kidney.