title: Effects of hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan on pulmonary function assessments.
abstract: High doses of tumor necrosis factor-alpha (TNF) seem to be effective in the treatment of solid tumors in the extremities. By applying current intensive care technology, systemic administration of high doses of TNF levels might be feasible for the treatment of cancer in other localizations. To establish the early and late effects of high systemic TNF levels on the lungs, we determined lung function parameters in 12 patients before and after hyperthermic isolated limb perfusion (HILP) with TNF and melphalan. Because of leakage during perfusion, mean maximum systemic TNF levels of 60.0 ng/ml (range, 0.3-356 ng/ml) were obtained. Significant alterations in the vital capacity (VC), the capillary blood volume (Vc), the diffusing capacity of the alveolocapillary membrane (Dm), and the transfer capacity of the lungs for carbon monoxide per unit alveolar volume (KCO) were observed 1 week after HILP. Eight weeks after HILP, they returned to pretreatment value. Alterations in lung functions were not related to the maximum systemic TNF level. In conclusion, disturbances in pulmonary functions are observed in patients after HILP with TNF and melphalan. These disturbances, which are probably partly caused by high systemic TNF levels, are reversible and would not preclude administration of systemic TNF in high doses.
authors.affiliation: Division of Medical Oncology, University Hospital Groningen, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Sleijfer
authors.forename: R J
authors.initials: RJ
authors.lastname: van Ginkel
authors.forename: T W
authors.initials: TW
authors.lastname: van der Mark
authors.forename: H J
authors.initials: HJ
authors.lastname: Hoekstra
authors.forename: J H
authors.initials: JH
authors.lastname: Zwaveling
authors.forename: H
authors.initials: H
authors.lastname: Schraffordt Koops
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
mesh_terms: D000328:Adult; D000368:Aged; D001132:Arm; D001943:Breast Neoplasms / Q000503:physiopathology / Q000601:surgery; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007866:Leg; D008297:Male; D008408:Mastectomy / Q000009:adverse effects; D008545:Melanoma / Q000188:drug therapy / Q000503:physiopathology; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D012129:Respiratory Function Tests; D012509:Sarcoma / Q000188:drug therapy / Q000503:physiopathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan