Management of  pegylated  interferon alpha toxicity in adjuvant therapy of melanoma.
BACKGROUND
Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma.


METHODS
This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature.


CONCLUSIONS
The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.
University of California, San Francisco, Melanoma Program, San Francisco 1600 Divisadero St, Rm A741, Box 1770, San Francisco, CA 94115, USA. adaud@medicine.ucsf.edu
Adil
A
Daud
Christopher
C
Soon
Reinhard
R
Dummer
Alexander M M
AM
Eggermont
Wen-Jen
WJ
Hwu
Jean Jacques
JJ
Grob
Claus
C
Garbe
Axel
A
Hauschild
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008545:Melanoma / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b