In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 118-118
Abstract:
118 Background: Imatinib plasma levels may be affected by the duration of exposure to imatinib and resection of the stomach. Therefore, we performed PK study to monitor imatinib plasma levels serially in the multinational phase II trial of perioperative imatinib for pts with large ( ≥ 10 cm) gastric GISTs without distant metastasis. Methods: In this trial conducted in Japan and Korea, 53 pts received neoadjuvant imatinib 400 mg daily and 40 pts received adjuvant imatinib after surgery. Blood samples for imatinib trough levels (Cmin) were collected after 1, 3, 6 months of each neoadjuvant and adjuvant imatinib and measured by using liquid chromatography-tandem mass spectrometry. For the comparison of imatinib Cmin between different time points, values were dose-adjusted and log-transformed. Results: During the neoadjuvant treatment, imatinib Cmin (mean ± standard deviation) was 2253.0 ± 1148.0 ng/mL (n = 49), 1623.3 ± 832.4 ng/mL (n = 47), and 1852.0 ± 1572.4 ng/mL (n = 45) after 1, 3, and 6 months of imatinib, respectively. During the postoperative treatment, imatinib Cmin was 1436.1 ± 852.8 ng/mL (n = 31), 1357.8 ± 646.4 ng/mL (n = 33), and 1084.2 ± 360.8 ng/mL (n = 31) after 1, 3, and 6 months of imatinib, respectively. In the neoadjuvant setting, imatinib Cmin was significantly reduced after 3 months (p = 0.0001) and 6 months (p = 0.004) compared to the value at 1 month. In 36 patients that imatinib Cmin was measured at both preoperative and postoperative setting, imatinib Cmin was significantly reduced after surgery (1732.4 ± 997.9 ng/mL vs 1282.8 ± 557.3 ng/mL; p = 0.04). The magnitude of changes in imatinib Cmin after surgery was greatest in patients who underwent total gastrectomy (10.6%, n = 2) followed by proximal gastrectomy (8.4%, n = 3), and wedge resection (3.3%, n = 30). There were no significant relationships between imatinib Cmin and toxicity or objective response. Conclusions: Imatinib exposure was reduced until approximately 3 months after imatinib treatment. It was also significantly reduced after surgery and the magnitude of changes might be affected by the extent of surgical resection of stomach.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.4_suppl.118
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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