INTRAPERITONEAL INFUSION OF RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR AND MITOXANTRONE IN NEOPLASTIC ASCITES - A FEASIBILITY STUDY

In cancers limited to the abdominal cavity the intraperitoneal adminis tration of antineoplastic drugs could be the treatment of choice becau se of both the limited systemic toxicity and the pharmacokinetic advan tage. Preclinical studies suggest that the combination of Tumor Necros is Factor (TNF) and mitoxantrone have a synergistic effect. On this ba sis, we conducted a study to verify the feasibility of the intraperito neal administration of these drugs in patients with malignant ascites. Cohorts of three patients were treated with a fixed dose of mitoxantr one (6 mg/m2) and escalating doses of TNF (from 60 up to 200 mcg/m2), intraperitoneally, given for two hours once a week for at least four w eeks. Seventeen patients with malignant ascites entered into the study . All but two patients received the planned four cycles. Sixty-six cyc les were given. The most common side effects were: fever (21-44% of cy cles), chills (8-44%), fatigue (19-33%), loss of appetite (17-57%), ma laise (25-43%), myalgia (33%), pain injection (25-83%), nausea/vomitin g (33-64%). Severe fatigue, malaise and anorexia were observed only at doses of 200 mcg/m2 of TNF. Weekly intraperitoneal administration of mitoxantrone (6 mg/m2) and TNF (200 mcg/m2) is a feasible regimen with acceptable toxicity. The activity of this combination should be studi ed in properly designed phase II trials.