Abstract
Imatinib is the standard first line treatment for chronic myeloid leukemia (CML). Owing to dose-related toxicities of Imatinib such as neutropenia, there is scope for treatment optimization through therapeutic drug monitoring (TDM). Trough concentration of 1 μg/mL is considered the therapeutic threshhold. Existing methods for the detection of Imatinib in plasma are limited by long read out time and expensive instrumentation. Hence, Raman spectroscopy was explored as a rapid and objective tool for monitoring Imatinib concentration. Three approaches: conventional Raman spectroscopy (CRS), Drop coating deposition Raman (DCDR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) were employed to detect the required trough concentration of 1 μg/mL and above. Detection of therapeutically relevant concentrations (1 μg/mL) using SERS and suitable nanoparticle substrates has been demonstrated. Prospectively, rigorous validation using clinical samples is necessary to confirm the utility of this approach in routine clinical usage.
Highlights
Tyrosine kinase inhibitors revolutionized the concept of well-tolerated cancer therapy with the introduction of Imatinib for therst line treatment of chronic phase chronic myeloid leukemia (CML)
Owing to the exposure e®ect relationship, Imatinib is an ideal candidate for therapeutic drug monitoring (TDM),[5] that would allow for optimization of dose to achieve improved molecular response in CML.[6]
This paper introduces the utility of Raman spectroscopy as a prospective tool for rapid monitoring of patients treated with Imatinib, at the therapeutic concentration of 1 g/mL and above
Summary
Tyrosine kinase inhibitors revolutionized the concept of well-tolerated cancer therapy with the introduction of Imatinib for therst line treatment of chronic phase chronic myeloid leukemia (CML). Imatinib inhibits ABL and the BCR-ABL fusion protein, c-KIT, and the platelet-derived growth factor receptor (PDGF-R).[1] It is used for the treatment of Philadelphia positive acute lymphoblastic leukemia (ALL), gastrointestinal stromal tumors (GIST) and some cases of dermatobrosarcoma protuberans. The standard dose used in adults is 400 mg once daily, whereas children with Philadelphia chromosome-positive leukemia receive a standard daily dose of 340 mg/m2.2 Trough Imatinib plasma concentrations above 1 g/mL are associated with complete cytogenetic and major molecular responses to standard dose (400 mg once daily) in chronic myeloid leukemia.[3] Variations in drug disposition, especially plasma clearance (CL), may result in excessive toxicity or suboptimal anticancer e±cacy. Liquid chromatography mass spectrometry (LC-MS) and high performance liquid chromatography (HPLC) are widely used and clinically practiced methods for the detection of Imatinib levels.[7]
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