Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum |
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| Authors: | J E Moulder J S Holcenberg B A Kamen M Cheng B L Fish |
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| Affiliation: | 1. Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI USA;2. Pediatrics, Los Angeles Children''s Hospital, Los Angeles, CA, USA;3. Pediatrics, University of Texas Health Science Center, Dallas, TX USA;4. Pathology, Los Angeles Children''s Hospital, Los Angeles, CA, USA;1. Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea;2. Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;3. Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea;4. Division of Hematology-Oncology, Keimyung University, School of Medicine, Keimyung University Hospital, Daegu, Republic of Korea;5. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea;6. Department of internal medicine, Inje university college of medicine, Haeundae Paik hospital, Busan, Republic of Korea;7. Department of Internal Medicine, Division of Hemato-Oncology, Inje University Busan Paik Hospital, Busan, Republic of Korea;8. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;9. Division of Hematology-Oncology, Kosin University Gospel Hospital, Busan, South Korea;10. Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea;11. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea;1. Department of Neurofarba, University of Studies of Florence, Italy;2. Paediatric Rheumatology, Hospital Anna Meyer, Florence, Italy;3. Centre for Pediatric and Adolescence Rheumatology, An der Schön Klinik, Hamburg Eilbek, Germany;4. Paediatric Rheumatology, Hospital Sant Joan de Déu, Barcelona, Spain;1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;2. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas;3. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas;4. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas;5. Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas;1. Department of Respiratory Medicine, Ichinomiya-nishi Hospital, Ichinomiya, Japan;2. Department of Radiology, Ichinomiya-nishi Hospital, Ichinomiya, Japan;1. Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China;2. Department of First Clinical Medical College, Nanjing Medical University, Nanjing 210000, Jiangsu Province, China |
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| Abstract: | We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity. |
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