Effect of sequencing on combined toxicity of renal irradiation and cisplatin.
We are using a rat model to study the effects of sequencing on the combined toxicity of renal irradiation and cisplatin (cis-Pt). Unanesthetized female WAG/RijMCW rats were given bilateral kidney irradiation (20 Gy in 9 fractions), preceded or followed by single ip doses of cis-Pt. Renal irradiation causes an increase in the acute toxicity of cis-Pt given 3-9 months after irradiation. Low-dose cis-Pt given immediately before irradiation, or as long as 9 months after irradiation, causes a decrease in the latent period for radiation nephritis and an increase in its severity. When given 3.7 to 7.7 months prior to irradiation, cis-Pt has a less severe effect on radiation nephritis. The greatest enhancement of radiation nephritis is seen for cis-Pt given 3 months after irradiation. Additive effects of cis-Pt and radiation on renal function can explain much, but not all, of the combined toxicity.
Moulder
J E
JE
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226.
Fish
B L
BL
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D003131:Combined Modality Therapy / Q000379:methods; D003404:Creatinine / Q000652:urine; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000528:radiation effects*; D011829:Radiation Dosage; D051381:Rats; D013997:Time Factors
D003404:Creatinine; D002945:Cisplatin