Treatment of a GIST patient with modified dose of sunitinib by measurement of plasma drug concentrations
Treatment of a GIST patient with modified dose of sunitinib by measurement of plasma drug concentrations
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DOI：
10.3892/ol.2012.779
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发表时间：
2012-09-01
期刊：
影响因子：
2.9
通讯作者：
Ohmori, Shigeru
中科院分区：
文献类型：
--
作者：
Hashita, Tadahiro;Katsuyama, Yoshihiko;Ohmori, Shigeru
在这项研究中，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和严重不良反应。1例60岁女性小肠GIST患者服用舒尼替尼50 mg/d治疗1周后，出现严重的血小板减少症(1.7x10(4)/亩L)。尽管舒尼替尼的剂量减少到每天25毫克，但血小板水平仍然很低。第7天，舒尼替尼+SU12662的谷浓度为4~6.1 ng/ml，曲线下面积为1,393.0ng.h/L，再次降至12.5 mg/d。然而，在恢复治疗的第二天，患者因舒尼替尼引起的心肌梗死而出现左心衰竭症状。据报道，舒尼替尼在体内的浓度范围为50-100 ng/ml(舒尼替尼加SU12662)，可抑制血小板衍生生长因子受体(PDGFR)的磷酸化。在这种情况下，血浆浓度足以抑制PDGFR在25或50毫克/天。然而，在两种剂量下都出现了血小板减少。虽然在这种情况下的结果并不表明血小板减少与血浆浓度之间存在相关性，但减少剂量可降低血小板减少的程度。综上所述，本文报道的结果表明，舒尼替尼联合SU12662的血药浓度是减少不良反应的重要指标。
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 (1.7x10(4)/mu l) 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 4-6.1 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.