Individualized pazopanib dosing : A prospective feasibility study in cancer patients
- Verheijen, Remy B.
- Bins, Sander
- Mathijssen, Ron H J
- Lolkema, Martijn P.
- Van Doorn, Leni
- Schellens, Jan H M
- Beijnen, Jos H.
- Langenberg, Marlies H G
- Huitema, Alwin D R
- Steeghs, Neeltje
DOIAbstract
Purpose: Pazopanib is a tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Retrospective analyses have shown that an increased median progression-free survival and tumor shrinkage appear in patients with higher plasma trough levels (Cmin). Therefore, patients with low Cmin might benefit from pharmacokinetically guided individualized dosing. Experimental Design: We conducted a prospective multicenter trial in 30 patients with advanced solid tumors. Pazopanib Cmin was measured weekly by LC-MS/MS. At weeks 3, 5, and 7, the pazopanib dose was increased if the measured Cmin was <20 mg/L and toxicity was <grade 3. Results: In total, 17 patients had at least one Cmin <20 mg/L at weeks 3, 5, and 7....
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