Open AccessCan therapeutic drug monitoring increase the safety of Imatinib in GIST patients?
Author(s) -
Zhuang Wei,
Xie JingDun,
Zhou Shan,
Zhou ZhiWei,
Zhou Yi,
Sun XiaoWei,
Yuan XiuHong,
Huang Min,
Liu Si,
Xin Shuang,
Su QiBiao,
Qiu HaiBo,
Wang XueDing
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1286
Subject(s) - imatinib , cmin , therapeutic drug monitoring , medicine , trough concentration , gist , metabolite , cmax , adverse effect , pharmacology , pharmacokinetics , gastroenterology , stromal cell , myeloid leukemia
Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST . The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (C min ) with adverse effects ( AE s) was described here. Plasma samples were obtained from patients after 3 months treatment with Imatinib (steady state, n = 122). Liquid chromatography/ tandem mass spectrometry was used to determine the concentration of Imatinib and its metabolite NDI . The incidence of myelosuppression was increased significantly with the increased Imatinib trough plasma concentration. The plasma level of Imatinib and NDI in patients who developed myelosuppression are 1698.3 ± 598.6 ng/ mL and 242.1 ng/ mL , respectively, which were significantly higher than those in patients who did not (1327.2 ± 623.4 ng/ mL , P = 1.75 × 10 ‐4 ; 206.3 ng/ mL , P = 0.006). Estimated exposure thresholds of Imatinib and NDI were 1451.6 ng/ mL with ROC AUC (95% CI ) of 0.693 (0.597–0.789) and 207.1 ng/mL with ROC AUC (95% CI ) of 0.646 (0.546–0.745), respectively. Multivariate regression confirmed the correlation of Imatinib C min with myelosuppression. Other side effects such as fluid retention and rash were not found to be correlated with Imatinib concentrations. These results suggest that trough concentration of Imatinib should be taken into consideration to increase the safety of Imatinib therapy in GIST patients.