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.