L. Delmastro et al., INTRAPERITONEAL INFUSION OF RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR AND MITOXANTRONE IN NEOPLASTIC ASCITES - A FEASIBILITY STUDY, Anticancer research, 15(5), 1995, pp. 2207-2212
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.