title: Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma.
abstract: Interleukin (IL-4) is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 micrograms/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 micrograms/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 micrograms/m2. One complete response occurred in a patient with metastatic melanoma (duration > or = 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.
authors.affiliation: City of Hope National Medical Center, Department of Medical Oncology, Duarte, California 91010-0269.
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: F R
authors.initials: FR
authors.lastname: Aronson
authors.forename: M
authors.initials: M
authors.lastname: Sznol
authors.forename: M B
authors.initials: MB
authors.lastname: Atkins
authors.forename: R
authors.initials: R
authors.lastname: Gucalp
authors.forename: R I
authors.initials: RI
authors.lastname: Fisher
authors.forename: M
authors.initials: M
authors.lastname: Sunderland
authors.forename: J H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: M L
authors.initials: ML
authors.lastname: Ernest
authors.forename: J W
authors.initials: JW
authors.lastname: Mier
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D015847:Interleukin-4