Severe adverse events frequently occur in patients treated with pazopanib, necessitating dose reduction and discontinuation. However, information on the exposure-toxicity relationship is limited.
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.
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 μg/mL (area under the curve, 0.85; 95% confidence interval, 0.70-0.99; P < .05). In the pazopanib < 20.5 μg/mL group (n = 3), no patient experienced an objective response. Objective response rates between patients with 20.5 to 50.3 μg/mL pazopanib (n = 11) and patients with ≥ 50.3 μg/mL (n = 13) were similar (45.5% vs. 46.2%).
From results of this study, the target trough pazopanib concentration range may be 20.5 to 50.3 μg/mL for patients with renal cell carcinoma.
Clinical genitourinary cancer. 2018 Dec 07 [Epub ahead of print]
Satoshi Noda, Tetsuya Yoshida, Daiki Hira, Ryosuke Murai, Keiji Tomita, Teruhiko Tsuru, Susumu Kageyama, Akihiro Kawauchi, Yoshito Ikeda, Shin-Ya Morita, Tomohiro Terada
Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan., Department of Urology, Shiga University of Medical Science Hospital, Shiga, Japan., Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan; College of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan., Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan. Electronic address: .