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.