title: Safety of pegylated interferon-alpha-2a in adjuvant therapy of intermediate and high-risk melanomas.
abstract: Pegylated (PEG)-IFN-alpha-2a is a modified form of recombinant human IFN-alpha-2a with sustained absorption and prolonged half-life. Our aim was to evaluate its safety profile in adjuvant treatment of high-risk melanoma patients in a single centre setting and to compare this safety profile with data obtained from the literature for a) low dose IFN-alpha and b) high dose IFN. Eighteen consecutive melanoma patients (AJCC 2002 stages IIa-IIIc) were retrospectively analyzed for toxicities associated with adjuvant PEG-IFN-alpha-2a (180 microg/week s.c.). The most frequently reported adverse events were constitutional side effects (78%), myelosuppression (83%) and hepatotoxicity (78%). The proportion of patients receiving PEG-IFN-alpha-2a and suffering from myelosuppression and liver toxicity was significantly higher than for patients reported in the literature undergoing low-dose IFN-alpha treatment (P = 0.008, P = 0.001 respectively), while fatigue and depression were seen less frequently with PEG-IFN-alpha-2a. By contrast, compared to patients treated with high-dose IFN-alpha, PEG-IFN-alpha-2a treated patients less frequently experienced fatigue (P < 0.001), neutropenia (P < 0.068) and neuropsychiatric (statistically not significant) adverse events. In conclusion, subcutaneously delivered PEG-IFN-alpha-2a is well tolerated in a once-weekly dose of 180 mug by most patients with high risk malignant melanoma. The frequency of side effects is increased compared to low dose, but reduced compared to high dose standard IFN-alpha. Due to its pharmacokinetic properties, pegylated IFN-alpha has, as in the treatment of hepatitis C, potential for increased efficacy in adjuvant therapy of melanoma.
authors: Department of Dermatology, University of Mainz, Mainz, Germany.
authors: Carmen
authors: C
authors: Loquai
authors: Dorothee
authors: D
authors: Nashan
authors: Peter
authors: P
authors: Hensen
authors: Thomas A
authors: TA
authors: Luger
authors: Stephan
authors: S
authors: Grabbe
authors: Cord
authors: C
authors: Sunderkötter
authors: Meinhard
authors: M
authors: Schiller
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a