Dosage Adjustment to Increase Plasma Trough Levels Requires Investigation for Treatment of RCC and Sarcoma

Individualized dosing should be studied to gauge whether subjectively increasing plasma trough levels of the tyrosine kinase inhibitor, pazopanib, has an impact on treatment of renal cell carcinoma (RCC) and soft tissue sarcoma (STS), according to a study published in Clinical Cancer Research.¹

Researchers enrolled 30 patients with solid tumors to this multicenter study, which was developed to determine whether patients with low trough levels could have an adjusted dose to increase the levels. High trough levels are linked to increased progression-free survival and tumor shrinkage.

Trough levels of pazopanib were measured weekly using liquid chromatography–mass spectrometry; dosage was increased every 2 weeks if trough levels were lower than 20 mg/L and toxicity was lower than grade 3.

Seventeen patients required dosage escalation; 10 were successfully treated; mean increase in trough levels was 13.2 mg/L to 22.9 mg/L; 9 patients with a mean high trough level of 51.3 mg/L had grade 3 or higher toxicities, and required a reduction of dose; trough levels in these patients, however, remained higher than the 20mg/L threshold.

The authors concluded that subjective dosing of pazopanib is possible, though more study is required to determine whether such increases lead to greater clinical efficacy for the treatment of RCC and STS.

Reference

1. Verheijen RB, Bins S, Mathijssen RH, et al. Individualized pazopanib dosing: a prospective feasibility study in cancer patients. Clin Cancer Res. 7 Jul 2016. doi: 10.1158/1078-0432.CCR-16-1255 [Epub ahead of print]