title: Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy.
abstract: A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.
authors.affiliation: Department of Hematology and Oncology, MHH University Medical Center Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schomburg
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: E
authors.initials: E
authors.lastname: Lopez-Hänninen
authors.forename: T
authors.initials: T
authors.lastname: Menzel
authors.forename: P
authors.initials: P
authors.lastname: Rudolph
authors.forename: A
authors.initials: A
authors.lastname: Körfer
authors.forename: M
authors.initials: M
authors.lastname: Fenner
authors.forename: H
authors.initials: H
authors.lastname: Poliwoda
authors.forename: J
authors.initials: J
authors.lastname: Atzpodien
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D001798:Blood Proteins / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D002802:Cholinesterases / Q000097:blood; D004796:Clinical Enzyme Tests; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D010045:Outpatients; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D000637:Transaminases / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001798:Blood Proteins; D007370:Interferon Type I; D007376:Interleukin-2; D008055:Lipids; D011994:Recombinant Proteins; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000637:Transaminases; D002802:Cholinesterases; D000469:Alkaline Phosphatase; D001663:Bilirubin