Regional pharmacokinetic selectivity of intraperitoneal cisplatin in ovarian cancer

Five patients with intraabdominal ovarian cancer, 4 of whom with concomitant ascites, refractory to cisplatin-containing combination chemotherapy were treated with intraperitoneal cisplatin. Cisplatin, 90 mg/m2, was administered intraperitoneally in 2 liters of warm 0.9% NaCl with a 4-hour dwelling time on day 1 q 21 days. Platinum concentrations in plasma, ascites, ultrafiltrates of plasma and ascites, and urine were assayed by flameless atomic absorption spectrophotometry and determinations were verified by neutron activation analysis. Peak total and ultrafiltrable plasma platinum levels were 1.63 +/- 0.6 and 0.76 +/- 0.3 microgram/ml, respectively. Peritoneal clearance of total platinum (PA) was 21 ml/min whereas body clearance of total platinum was on the average 13.8 times PA, varying from 171 to 429 ml/min; the mean AUC (peritoneum) to AUC (plasma) ratio was 11 +/- 3. In 2 patients control of ascites was obtained, in 1 of these patients prior positive cytology became negative after her first intraperitoneal course. No nephrotoxicity was observed and gastrointestinal toxicity was mild. No catheter-related infections were observed. Intraperitoneal cisplatin therapy is well tolerated, pharmacokinetically rational and may be useful in managing ovarian cancer patients with malignant ascites or minimal residual disease at second-look laparotomy.