Pazopanib Tolerability When Given With Food

Summary

Pazopanib (Votrient) is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg once daily (OD) regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of \~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A reduced dose taken with food could be a possible approach to reduce these side effects. Therefore the investigators initially want to determine the equivalent reduced dose of pazopanib when taken with a continental breakfast. Thereafter the investigators want to investigate whether the intake with food reduces the frequently reported side effects nausea and diarrhea.

Timeline

Start

2014-06

Primary completion

2018-11

Completion

2018-11

Publications

• Results Lubberman FJE, Gelderblom H, Hamberg P, Vervenne WL, Mulder SF, Jansman FGA, Colbers A, van der Graaf WTA, Burger DM, Luelmo S, Moes DJAR, van Herpen CML, van Erp NP. The Effect of Using Pazopanib With Food vs. Fasted on Pharmacokinetics, Patient Safety, and Preference (DIET Study). Clin Pharmacol Ther. 2019 Nov;106(5):1076-1082. doi: 10.1002/cpt.1515. Epub 2019 Jul 9.
• Krens SD, Lubberman FJE, van Egmond M, Jansman FGA, Burger DM, Hamberg P, Vervenne WL, Gelderblom H, van der Graaf WTA, Desar IME, van Herpen CML, van Erp NP. The impact of a 1-hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure. Int J Cancer. 2021 Jun 1;148(11):2799-2806. doi: 10.1002/ijc.33469. Epub 2021 Jan 19.

Drugs

Indications