Serum concentrations of pegylated interferon alpha-2b in patients with resected stage III melanoma receiving adjuvant pegylated interferon alpha-2b in a randomized phase III trial (EORTC 18991).
OBJECTIVE
The EORTC 18991 trial assessed the effect of long-term adjuvant pegylated interferon (Peg-IFN) alpha-2b administered weekly in patients with lymph node-positive melanoma. Serum concentrations were analyzed to determine exposure to Peg-IFN alpha-2b.


METHODS
After surgery, patients were randomized to receive Peg-IFN alpha-2b or to observation only. The treatment group received 6 microg/kg/week Peg-IFN alpha-2b subcutaneously for 8 weeks, followed by a maintenance dose of 3 microg/kg/week for up to 5 years. Blood samples were collected between months 3 and 60.


RESULTS
A total of 208 Peg-IFN alpha-2b concentrations from 48 patients were available. Serum trough concentrations increased in a dose-related manner. Mean dose-normalized serum concentrations and intersubject variability over the 5-year study period in patients with melanoma were similar to those observed in patients with chronic hepatitis.


CONCLUSIONS
Data suggest that the exposure to Peg-IFN alpha-2b was sustained during long-term adjuvant treatment with Peg-IFN alpha-2b in patients with melanoma, consistent with the EORTC 18991 trial's conclusion of a significant, sustained, and relapse-free survival benefit.
Eggermont
Alexander M M
AM
Department of Surgical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, 310 Groene Hilledijk, 3075 EA, Rotterdam, The Netherlands. a.eggermont@erasmusmc.nl
Bouwhuis
Marna G
MG
Kruit
Wim H
WH
Testori
Alessandro
A
ten Hagen
Timo
T
Yver
Antoine
A
Xu
Christine
C
D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000097:blood* / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b