Exploratory Investigation of Target Pazopanib Concentration Range for Patients With Renal Cell Carcinoma

A trough pazopanib concentration of >= 20.5 mu g/mL is required for effective treatment for patients with renal cell carcinoma. However, the toxic concentration of pazopanib remains unknown. We reported pazopanib of >= 50.3 mu g/mL led to severe toxicity. Consequently, we proposed that the target range of pazopanib is a trough concentration from 20.5 to 50.3 mu g/mL. Background: Severe adverse events frequently occur in patients treated with pazopanib, necessitating dose reduction and discontinuation. However, information on the exposure-toxicity relationship is limited. Patients and Methods: For this retrospective and observational clinical study, we examined 27 patients with renal cell carcinoma treated with pazopanib and enrolled between October 2014 and March 2018. The primary goal was to evaluate the association between trough pazopanib concentration and occurrence of grade >= 3 toxicities, and secondarily, to estimate the association between trough pazopanib concentration and objective response rate. Results: Mean trough pazopanib concentration was significantly higher in the grade >= 3 toxicity group (n = 9) than in the grade <= 2 toxicity group (n = 18). Based on the receiver operating characteristic curve, the threshold value of trough pazopanib concentration for predicting grade >= 3 toxicities was 50.3 mu g/mL (area under the curve, 0.85; 95% confidence interval, 0.70-0.99; P < .05). In the pazopanib < 20.5 mu g/mL group (n = 3), no patient experienced an objective response. Objective response rates between patients with 20.5 to 50.3 mu g/mL pazopanib (n = 11) and patients with >= 50.3 mu g/mL (n = 13) were similar (45.5% vs. 46.2%). Conclusion: From results of this study, the target trough pazopanib concentration range may be 20.5 to 50.3 mu g/mL for patients with renal cell carcinoma. (C) 2018 Elsevier Inc. All rights reserved.