The crushed form of pazopanib, an oral inhibitor of vascular endothelial growth factor receptors (VEGFRs), was safe and effective in 2 case reports described in the Journal of Oncology Pharmacy Practice.1
Pazopanib is an oral inhibitor of VEGFR-1, -2, and -3, as well as other tyrosine kinases, that was approved by the US Food and Drug Administration (FDA) for the treatment of advanced renal cell carcinoma and advanced soft tissue sarcoma in patients who have received prior chemotherapy.2 It is available as a 200 mg tablet; the recommended starting dose is 800 mg once daily without food. This drug is not typically given to patients who cannot swallow the tablet whole because the crushed formulation has been associated with increased drug exposure. Despite this, crushed pazopanib was shown to be safe and effective in these patients who could not swallow the tablet whole.
The first case involved a 71-year-old Caucasian woman with metastatic renal cell carcinoma who experienced disease progression following lines of therapy with intravenous bevacizumab, temsirolimus, and nivolumab, as well as dissolved oral axitinib and open capsules of oral sunitinib. Because she could not swallow pills, she was treated with 400 mg of crushed pazopanib mixed in applesauce and taken on an empty stomach. The pazopanib dose was subsequently increased to 600 mg. Although the patient experienced moderate to severe dilation of the bile duct, grade 1 or 2 elevations in total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as grade 1 thrombocytopenia, she responded to the treatment and was able to continue pazopanib for 10 months until disease progression.
In the second case, a 43-year-old African American woman with chordoma, a type of soft tissue sarcoma, at the base of her skull was treated with crushed pazopanib at an initial dose of 200 mg mixed in applesauce and taken on an empty stomach. The dose was increased incrementally by 200 mg every 2 weeks until a final dose of 800 mg, mixed in yogurt, was reached. The patient developed skin hypopigmentation, hypothyroidism, and fatigue, but these adverse effects were treated and she was able to continue the full dose. At 3 months, the dose was reduced to 600 mg due to grade 2 diarrhea and fatigue. Pazopanib was withheld for 1 week during the following month due to grade 3 diarrhea; however, it was subsequently restarted at 600 mg. The patient tolerated the therapy well at a dose of 600 mg administered on all but 4 or 5 consecutive days a month, and experienced stable disease for 2.5 years.
“Although crushing pazopanib is not routinely recommended, we demonstrate the feasibility of using the crushed form when medically necessary and no suitable alternatives exist, with careful safety monitoring and dose adjustments accordingly,” the researchers noted.
1. Stein J, Milhem M, Vaena D. Clinical outcomes and toxicities of pazopanib administered orally in crushed form: Case reports and review of the literature [published online April 8, 2019]. J Oncol Pharm Pract. doi: 10.1177/1078155219841108
2. Votrient® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.