Treating cancer with PEG intron - Pharmacokinetic profile and dosing guidelines for an improved interferon-alpha-2b formulation

BACKGROUND. PEG Intron (pegylated interferon-alpha-2b [IFN-alpha-2b]; Schering-Plough, Kenilworth, NJ) has demonstrated delayed clearance and increased area under the curve compared with native IFN-alpha-2b. Studies in patients with chronic hepatitis C infection and malignancies have demonstrated both biologic and clinical activity of PEG Intron and have provided empiric data to compare the pharmacokinetics (PK) and pharmacodynamics of PEG Intron and IFN-alpha-2b. METHODS. The authors conducted a review of the available data comparing the PK and pharmacodynamic effects of PEG Intron and IFN-alpha-2b. Safety and efficacy data from Phase I/II studies of PEG Intron in patients with chronic myelogenous leukemia (CML) and solid tumors were also reviewed. RESULTS. Data from patients with chronic hepatitis C infection suggest that exposure to IFN at a PEG Intron dose of 0.25 mug/kg per week is similar to that observed after administration of IFN-alpha-2b at a dose of 3 million International Units, three times per week. PEG Intron at doses up to 6 mug/kg per week was well tolerated and demonstrated clinical activity in patients with CML and solid tumors, including metastatic melanoma and renal cell carcinoma. CONCLUSIONS. Dose intensification can be achieved safely in patients with CML and solid tumors using PEG Intron, which could improve efficacy. These results provide useful dosing guidelines to clinicians investigating the antitumor activity of PEG Intron in patients with malignancies. More data are needed to determine the optimal dose in various oncologic indications. However, these results provide a sound rationale for further investigation of PEG Intron. (C) 2002 American Cancer Society.