Early postoperative intraperitoneal daily mitoxantrone. A feasibility and pharmacokinetic study

Fractionated doses have been advocated to prevent chemoperitonitis after intraperitoneal infusion of mitoxantro ne, particularly in operated patients. Twenty patients with peritoneal carcinomatosis underwent surgery, including intestinal resections, with minimal residual disease. Peritoneal mitoxantrone in 1000 mL/m2 saline was planned on the first postoperative day in groups of four patients (5 mg/m2 for 3 and 5 days, 7.5 mg/m2 for 3 and 4 days, 10 mg/m2 for 2 and 3 days). Pharmacokinetics were completed on the first day in five patients receiving 5 mg and in five patients receiving 10 mg, on the 5th day in three pa tients receiving 5 mg, and on the 3rd day in one patient receiving 10 mg . No major complications nor severe pain were observed. Myelosuppression was the dose limiting toxicity. Only one and three patients received the 7.5-mg 4-day and 10-mg 3-day regimen s, respectively. On the first day, the mean peritoneal peak concentrations of mitoxantrone were 1.45±0.56 (range 0.48-1.9) and 1.91± 0.85 (range 1.27-3.13) μ g/mL in the 5-mg and 10-mg patients, respectively. Mean dialysate/plasma exposure (AUC) ratio was 115 . Even in patients with sutures, early postoperative fractionated intraperitoneal mitoxantrone appears feasible and safe, with a high local advantage, for up to 5 days of treatment and a maximum tolerated total dose of 20-25 mg/m2.