Pegylated interferon-alpha2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pteridine plasma concentrations.
Our objective was to study the influence of pegylated interferon-alpha2b (PEG-IFN-alpha) on the metabolism of amino acids and pteridines. We used an exploratory study into plasma concentrations of large neutral amino acids, 5-hydroxyindolacetic acid (5-HIAA), total biopterin (BIOP) and neopterin (NEOP) in 40 high-risk melanoma patients. Patients were randomized to treatment with PEG-IFN-alpha once a week in a dose of 6 microg/kg/week s.c. during 8 weeks, followed by a maintenance treatment of 3 microg/kg/week s.c. or to observation only. We found that treatment with PEG-IFN-alpha decreases tryptophan (TRP) concentrations in the first 3 months of treatment to a maximum of 25.3% compared to controls [95% confidence interval (CI): 14.9 to 34.4]. The TRP:LNAA ratio, an index for the availability of TRP to the central nervous system (CNS), decreases during 6 months with 18.8% (95% CI: 11.9 to 25.2). Concentrations of NEOP rose; however, concentrations of BIOP, the sum of tetrahydrobiopterin [BH4] and its oxidative products, did not decrease. The ratio of phenylalanine to tyrosine was increased with 11.7% (95% CI: 1.0 to 23.5) during 6 months. We conclude that, like conventional IFN-alpha, PEG-IFN-alpha lowers TRP concentrations and decreases the availability of TRP to the CNS. PEG-IFN-alpha has a similar influence on pteridine metabolism as standard IFN-alpha. If a lowered availability of TRP and a consequent decrease of serotonergic neurotransmission are indeed a mechanism underlying neuropsychiatric side-effects of IFN-alpha, patients on PEG-IFN-alpha are not at a lower risk of developing neuropsychiatric side-effects as patients on conventional IFN-alpha.
Van Gool
Arthur R
AR
Department of Psychiatry, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. a.vangool@erasmusmc.nl
van Ojik
Heidi H
HH
Kruit
Wim H J
WH
Bannink
Marjolein
M
Mulder
Paul G H
PG
Eggermont
Alexander M M
AM
Stoter
Gerrit
G
Fekkes
Durk
D
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000187:drug effects / Q000378:metabolism*; D001708:Biopterins / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D019798:Neopterin / Q000378:metabolism; D010649:Phenylalanine / Q000187:drug effects / Q000378:metabolism; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011621:Pteridines / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D013997:Time Factors; D014364:Tryptophan / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011621:Pteridines; D011994:Recombinant Proteins; D001708:Biopterins; D011092:Polyethylene Glycols; D014443:Tyrosine; D010649:Phenylalanine; D006897:Hydroxyindoleacetic Acid; D019798:Neopterin; D014364:Tryptophan; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a