Dataset Information

Pharmacokinetic/pharmacodynamic analysis of adjuvant pegylated interferon ?-2b in patients with resected high-risk melanoma.

ABSTRACT:

Purpose

High-dose pegylated interferon ?-2b (peginterferon ?-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon ?-2b in patients with high-risk melanoma.

Methods

For PK analysis, 32 patients received peginterferon ?-2b 6 ?g/(kg week) subcutaneously for 8 weeks (induction) then 3 ?g/(kg week) for 4 weeks (maintenance). PK profiles were determined at weeks 1, 8, and 12. Exposure-response relationships between peginterferon ?-2b and absolute neutrophil count (ANC) and alanine aminotransferase (ALT) level were also studied.

Results

Peginterferon ?-2b was well-absorbed following SC administration, with a median T (max) of 24 h. Mean half-life estimates ranged from 43 to 51 h. The accumulation factor was 1.69 after induction therapy. PK parameters showed moderate interpatient variability. PK profiles were described by a one-compartmental model with first-order absorption and first-order elimination. Toxicity was profiled and was acceptable; observed side effects were similar to those previously described. Dose reduction produced proportional decreases in exposure and predictable effects on ANC in an Imax model; however, a PK/pharmacodynamic (PK/PD) relationship between peginterferon ?-2b and ALT could not be established with high precision.

Conclusions

Peginterferon ?-2b was well-absorbed and sustained exposure to peginterferon ?-2b was achieved with the doses tested. These data confirm and extend previous PK observations of peginterferon ?-2b in melanoma and solid tumors. Our PK/PD model of exposure and ANC effect provides useful information for prediction of peginterferon ?-2b-related hematologic toxicity.

SUBMITTER: Daud AI

PROVIDER: S-EPMC3043235 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Publications

Pharmacokinetic/pharmacodynamic analysis of adjuvant pegylated interferon α-2b in patients with resected high-risk melanoma.

Daud A I AI Xu C C Hwu W-J WJ Urbas P P Andrews S S Papadopoulos N E NE Floren L C LC Yver A A Deconti R C RC Sondak V K VK

Cancer chemotherapy and pharmacology 20100528 3

<h4>Purpose</h4>High-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon α-2b in patients with high-risk melanoma.<h4>Methods</h4>For PK analysis, 32 patients received peginterferon α-2b 6 μg/(kg week) subcutaneously for 8 weeks (induction) then 3 μg/(kg week) for 4 weeks (maintenance). PK profiles were determ ...[more]

PMID: 20509027

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