Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine in refractory ovarian cancer patients

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
S K ChambersG Pizzorno

Abstract

The feasibility and pharmacokinetics of cyclosporine (CsA) delivered intraperitoneally (IP) have not been previously explored. We performed a pharmacokinetic study of IP CsA followed by a phase I dose-escalation trial of the combination of IP CsA and carboplatin in refractory ovarian cancer patients. A pilot study was performed of three patients who received 1, 10, and 20 mg/kg IP CsA alone. Subsequently, a phase I trial of 35 patients was performed between April 1990 and April 1993. Whole-blood and IP fluid CsA concentrations were measured at serial time points. The highest dose delivered IP was 34.6 mg CsA/kg in combination with carboplatin (250 mg/m2 or 300 mg/m2, depending on creatinine clearance), which was not dose-escalated. The area under the concentration-time curve (AUC) for CsA and half-life (T1/2) were calculated. Objective and serologic responses were noted, and toxicity was graded using the National Cancer Institute common toxicity criteria. The feasibility of delivering IP CsA alone was established. We observed a 1,000:1 ratio between IP fluid and blood concentrations at 20 mg CsA/kg. Pharmacokinetic analysis confirmed that at 20 mg CsA/kg, there was an IP fluid-to-blood AUC ratio of 600:1 in favor of peritoneal ...Continue Reading

Citations

Mar 17, 2007·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·R J MorganJ H Doroshow
May 26, 2005·Journal of Feline Medicine and Surgery·Andy SparkesDominique Vanthournout
Feb 27, 1999·Current Opinion in Obstetrics & Gynecology·S MakhijaR R Barakat
Jun 9, 2004·Cancer Chemotherapy and Pharmacology·Robert J MorganJames H Doroshow
Aug 5, 2010·Journal of Agricultural and Food Chemistry·Chao-Yuan HuangTzyh-Chyuan Hour

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