Phase I Trials and Pharmacokinetic Studies of Intraperitoneal Cisplatin, Melphalan, Methotrexate, and Cytarabine

摘要: Phase I and pharmacokinetic studies of the intraperitoneal administration cisplatin, melphalan, methotrexate, cytarabine have been completed at UCSD Cancer Center. For all four agents, there is a very large pharmacologic advantage to via route. The mean ratio total drug exposure for peritoneal cavity plasma was 12.4 (range 2.9–37.4) 65 17–176) 92 7–303) 570 320–1000) cytarabine. dose-limiting toxicity agents systemic rather than local, dose administered into could be escalated point where amount leaking sytemic circulation provided equivalent that which obtained with intravenous injection. In case concurrent sodium thiosulfate excellent protection kidneys permitted escalation cisplatin 270 mg/m2. methotrexate cytarabine, it possible maintain concentrations well above minimal cytotoxic level ovarian carcinoma period five days acceptable toxicity. results indicate these drugs can repeatedly this route in great relative administration.