Possibility for dose optimization of pazopanib from its plasma concentration in Japanese patients with cancer

Abstract

The currently approved dose of pazopanib (800mg) is being re-examined owing to its adverse effects. The aim of this study was to evaluate the relationships among starting or maintenance doses of pazopanib, estimated pazopanib Cmin, and other clinical factors, including albumin and α-1 acid glycoprotein levels, in soft-tissue sarcoma and renal cell carcinoma. We also determined whether therapeutic drug monitoring of pazopanib concentrations may be used to improve its therapeutic efficacy and prevent adverse effects. Forty patients who received pazopanib for renal cancer or soft-tissue sarcoma at the Hokkaido Cancer Center were evaluated prospectively. Cmin for pazopanib was calculated based on the measured values from the plasma samples. The efficacy and time to treatment failure were then assessed. The pazopanib maintenance doses were 200 (n=4), 400 (n=34), 600 (n=4), and 800mg (n=1). Most patients (65%) who received a 400mg dose had an effective pazopanib concentration (≧20µg/mL), whereas 35% of patients who received the 400mg dose had ineffective concentrations (<20µg/mL). Logistic regression analysis revealed that only the albumin level was significantly associated with effective pazopanib concentrations (odds ratio: 1.37, p=0.0234). In conclusion, a dose of 400mg had been effective and well tolerated in more than half of patients in this study. However, therapeutic drug monitoring is necessary during pazopanib therapy.