title: The effects of oral pentoxifylline on interleukin-2 toxicity in patients with metastatic renal cell carcinoma.
abstract: Interleukin-2 (IL-2) mediates the regression of metastatic renal cell carcinoma, but clinical application has been limited by associated toxicities. Preclinical studies show that pentoxifylline (PTXF), a methylxanthine derivative, inhibits IL-2 toxicity while preserving anti-tumour efficacy. This study was designed to determine whether oral PTXF would alter IL-2-induced toxicities. Patients with disseminated renal cell carcinoma were treated with continuous infusion of 18 x 10(6) IU/m2/24 h for 4 days followed by 3 days without treatment, for 4 consecutive weeks. After a 2-week interval, the 4-week treatment cycle was repeated. All patients concomitantly received oral PTXF (2000 mg/24 h) in five divided doses. Despite the co-administration of PTXF, all patients demonstrated a spectrum and severity of toxicities consistent with previous reports of continuous infusion of IL-2 alone. There was considerably more nausea and vomiting associated with the administration of PTXF which improved on withdrawal of PTXF. Oral PTXF in IL-2 therapy did not show any substantiated benefit. Indeed, patients suffered more severe nausea and vomiting than if they had received IL-2 alone, resulting in the early termination of the trial.
authors.affiliation: Division of Surgical Oncology, University of Louisville School of Medicine, Kentucky 40292, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Anderson
authors.forename: T M
authors.initials: TM
authors.lastname: Woodcock
authors.forename: J I
authors.initials: JI
authors.lastname: Harty
authors.forename: A W
authors.initials: AW
authors.lastname: Knott
authors.forename: M J
authors.initials: MJ
authors.lastname: Edwards
mesh_terms: D000284:Administration, Oral; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000556:secondary; D009325:Nausea / Q000139:chemically induced; D010431:Pentoxifylline / Q000008:administration & dosage*; D017211:Treatment Failure; D014839:Vomiting / Q000139:chemically induced
chemical_list: D007376:Interleukin-2; D010431:Pentoxifylline