title: Intraperitoneal infusion of recombinant human tumor necrosis factor and mitoxantrone in neoplastic ascites: a feasibility study.
abstract: In cancers limited to the abdominal cavity the intraperitoneal administration of antineoplastic drugs could be the treatment of choice because of both the limited systemic toxicity and the pharmacokinetic advantage. Preclinical studies suggest that the combination of Tumor Necrosis Factor (TNF) and mitoxantrone have a synergistic effect. On this basis, we conducted a study to verify the feasibility of the intraperitoneal administration of these drugs in patients with malignant ascites. Cohorts of three patients were treated with a fixed dose of mitoxantrone (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 weeks. Seventeen patients with malignant ascites entered into the study. All but two patients received the planned four cycles. Sixty-six cycles were given. The most common side effects were fever (21-44% of cycles), chills (8-44%), fatigue (19-33%), loss of appetite (17-57%), malaise (25-43%), myalgia (33%), pain injection (25-83%), nausea/vomiting (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 studied in properly designed phase II trials.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Del Mastro
authors.forename: M
authors.initials: M
authors.lastname: Venturini
authors.forename: P G
authors.initials: PG
authors.lastname: Giannessi
authors.forename: A
authors.initials: A
authors.lastname: Vigani
authors.forename: O
authors.initials: O
authors.lastname: Garrone
authors.forename: F
authors.initials: F
authors.lastname: Carnino
authors.forename: P
authors.initials: P
authors.lastname: Russo
authors.forename: P
authors.initials: P
authors.lastname: Galletti
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001201:Ascites / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008942:Mitoxantrone