Hashita Tadahiro, Katsuyama Yoshihiko, Nakamura Katsunori, Momose Yasuyuki, Komatsu Daisuke, Koide Naohiko, Miyagawa Shinichi, Nakamura Tomonori, Yamamoto Koujirou, Ohmori Shigeru
Department of Pharmacy, Shinshu University Hospital, Matsumoto.
Oncol Lett. 2012 Sep;4(3):501-504. doi: 10.3892/ol.2012.779. Epub 2012 Jun 28.
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.
在本研究中，我们报告了舒尼替尼在一名患有胃肠道间质瘤（GIST）的女性患者中的药代动力学及严重不良反应。一名60岁患有小肠GIST的女性患者，在接受50mg/天舒尼替尼治疗1周后出现严重血小板减少（1.7×10⁴/μl）。尽管舒尼替尼剂量减至25mg/天，但血小板水平仍维持在低水平。第7天时，舒尼替尼加SU12662的谷浓度为46.1ng/ml，曲线下面积（AUC）为1393.0ng·h/l。剂量再次减至12.5mg/天。然而，恢复治疗后的第二天，患者因舒尼替尼引起的心肌病变出现左心衰竭症状。据报道，舒尼替尼在体内浓度超过50 - 100ng/ml（舒尼替尼加SU12662）范围时可抑制血小板衍生生长因子受体（PDGFR）磷酸化。在此病例中，血浆浓度在25mg/天或50mg/天时足以抑制PDGFR。然而，两种剂量下均出现了血小板减少。尽管该病例结果未提示血小板减少与血浆浓度之间存在相关性，但通过降低剂量，血小板减少程度有所减轻。总之，此处报告的研究结果表明，舒尼替尼加SU12662的血浆浓度是减少不良反应的重要指标。
