In this study we report the pharmacokinetics and severe adverse effects of sunitinib in a woman with a gastrointestinal stromal tumor (GIST). A 60-year-old woman with small intestinal GIST developed severe thrombocytopenia (1.7×10 4/μl) following 1 week of treatment with sunitinib at 50 mg/day. Although the dose of sunitinib was reduced to 25 mg/day, platelet levels remained low. On day 7, the trough concentration of sunitinib plus SU12662 was 46.1 ng/ml and the area under the curve (AUC) was 1,393.0 ng·h/l. The dose was again reduced to 12.5 mg/day. However, the day after resumption of treatment, the patient developed symptoms of left heart failure due to myocardosis caused by sunitinib. Sunitinib has been reported to inhibit platelet-derived growth factor receptor (PDGFR) phosphorylation at concentrations over the range of 50-100 ng/ml (sunitinib plus SU12662) in vivo. In this case, the plasma concentration was sufficient to inhibit PDGFR at 25 or 50 mg/day. However, thrombocytopenia appeared at both dosages. Although the results in this case did not suggest a correlation between thrombocytopenia and plasma concentration, the degree of thrombocytopenia was decreased by reduction of the dose. In conclusion, the findings reported here indicate that the plasma concentration of sunitinib plus SU12662 is an important indicator to reduce adverse effects.
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