Patients with gastrointestinal stromal tumors (GIST) had stable plasma concentrations of imatinib during long-term treatment, reported Yoon-Koo Kang, MD, PhD, and colleagues at the Gastrointestinal Cancers Symposium.
Patients with gastrointestinal stromal tumors (GIST) had stable plasma concentrations of imatinib during long-term treatment, reported Yoon-Koo Kang, MD, PhD, and colleagues at the Gastrointestinal Cancers Symposium. Comparison of baseline and follow-up laboratory values showed that trough levels (Cmin) of imatinib increased significantly (P <.001). Moreover, inter- and intra-subject variability declined from baseline to followup testing.
"Previous pharmacokinetic evaluation of patients with gastrointestinal stromal tumors had suggested that plasma concentrations of imatinib decrease following long-term exposure," said Kang, of the University of Ulsan in Seoul, South Korea, and colleagues. "In our study, steady-state imatinib trough levels did not decrease but remained stable in most GIST patients during long-term treatment." "Changes in imatinib Cmin were associated with changes in albumin concentration," he added. "Monitoring of imatinib Cmin only for concerns about time-dependent decreases in imatinib exposure is not necessary."
The findings came from a study involving 65 patients with GIST treated for at least 9 months with the same dose of imatinib. All but 4 patients received 400 mg/d and the rest were treated at a dose of 300 mg/d. Investigators obtained a total of 127 baseline blood samples and 117 samples at follow-up. Each sample underwent assessment of imatinib Cmin by liquid chromatography-tandem mass spectrometry. Baseline samples were obtained a median of 6.4 months after starting imatinib and the median interval from baseline to follow-up measurement was 13.1 months.
At baseline, imatinib Cmin averaged 1221 %uFFFD 624 ng/mL and increased to 1442 %uFFFD 693 ng/mL at follow-up (P <.001). The inter- and intrapatient variability averaged 49.2% and 25.5%, respectively, at baseline, compared with 44.2% and 20.4% at follow-up. Multivariate analysis showed a significant correlation between the baseline/ follow-up ratios of imatinib Cmin and albumin (P = .001).
Per-sample analysis showed that imatinib Cmin correlated significantly with age, hemoglobin, albumin, creatinine clearance, previous major gastrectomy, and the interval from baseline to follow-up measurement of plasma drug levels.
Kang YK, Yoo C, Ryoo B, et al. Changes in imatinib plasma trough level during long-term treatment of patients with advanced gastrointestinal stromal tumors. Paper presented at: 2011 Gastrointestinal Cancers Symposium; January 2011; San Francisco, CA.
Published in Oncology & Biotech News. February 2011.