Histological changes following high-dose methotrexate and cisplatinum administration and the influence of dosage scheduling.
Histological changes were studied in experimental animals following the intraperitoneal administration of high-dose cisplatin with or without high-dose methotrexate and citrovorum factor. There were pronounced renal toxicities with high-dose (10 mg/kg) cisplatin, particularly involving distal tubules with glomerular congestion. However, lower toxicities were noted with reduced dosage of cisplatin (5 mg/kg) and especially if given once as a single bolus injection instead of a 5-day regimen. Renal and hepatic toxicities were marked with concomitant methotrexate administration leading to hemorrhagic diathesis and shorter survival. However, toxicities were relatively reduced when cisplatin was given as a single bolus injection instead of a 5-day divided course. Such information may prove helpful in future planning of combination chemotherapy in patients with malignancies using these two agents.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D006474:Hemorrhagic Disorders / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats
D002945:Cisplatin; D008727:Methotrexate