Harnessing soft tissue sarcoma with low-dose pazopanib – a matter of blood levels

BACKGROUND: Pazopanib is a tyrosine kinase inhibitor indicated for the treatment of renal cell carcinoma and soft tissue sarcoma. Despite the high inter-patient variability in pharmacokinetic exposure, pazopanib is administered at a fixed dose of 800 mg once daily (QD). Pharmacokinetic exposure is linked to both efficacy and toxicity. In this case report, we illustrate the value of therapeutic drug monitoring by describing two patients with adequate pazopanib trough concentrations (C(min)) at an eight times lower than standard dose. CASE PRESENTATION: Patient A is a 69-year-old woman with metastatic leiomyosarcoma who had significant toxicities and a high C(min) on the standard dose. While dose reductions to 200 mg QD and later 200 mg every other day were made, pazopanib C(min) remained above the efficacy threshold. Patient B is a 50-year-old male with metastatic angiosarcoma and a history of Gilbert syndrome. Pazopanib treatment was initiated at the standard dose of 800 mg QD, but was reduced to 200 mg QD 1-week-on - 1-week-off due to total bilirubin elevation. Pazopanib C(min) was adequate in this patient as well. CONCLUSION: It could be valuable to measure pazopanib levels in case of dose reductions due to toxicity, as exposure could still be adequate at considerably lower than standard doses.