P-027 - Therapeutic drug monitoring of imatinib in GIST patients: a tunisian series

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
GIST
Presenter H. Meganem
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors H. Meganem1, S. Trabelsi2, A. Klouz1, M. Lakhal1
  • 1Medical Department of Abderrahmen Mami Hospital, Ariana/TN
  • 2Centre National de Pharmacovigilance, Tunis/TN

Abstract

Introduction

Gastrointestinal stromal tumors (GIST) are rare and their prognosis had dramatically changed since the advent of imatinib. Imatinib mesylate is a TKI given orally, daily. This route of administration exposes to large inter-individual variability in bioavailability, which could affect the efficacy and safety of this treatment. The therapeutic drug monitoring (TDM) of imatinib is recommended in some clinical situations to adjust dosage based on the plasma concentrations found.

Methods

Our work is a retrospective study about 40 plasmatic assays of imatinib in 33 patients followed for GIST, realized in the national center of pharmacovigilance from January 2010 to January 2014. The purpose was to demonstrate the advantage of TDM of imatinib by studying the inter-individual variability in plasma concentrations, and the correlation between imatinib dosage and it plasma trough level.

Results

There were 25 men and 8 women. At the time of the assays, they had a median age of 53 years [29- 76]. TDM of imatinib was motivated by the occurrence of adverse effects in 12 cases (30%), by obtaining a sub-optimal therapeutic response in 23 cases (57.5%) and by suspicion of poor compliance in 3 cases (7, 5%). Plasma assay was performed in average 14.02 months after the onset of imatinib treatment. At the time of the assay, 33 patients received imatinib at the dosage of 400mg / day, 5 received 800mg / day, 1 received 300mg / day and 1 600mg / day. Imatinib was used once daily in 34 cases, and twice in 6 cases. Eight patients received other treatments than imatinib. Imatinib plasma trough levels ranged from 151.7 ng / ml to 7414.3 ng / ml with a median of 1476.9 ng / ml.

No statistical significant correlation was found between imatinib trough level and age, sex, weight, imatinib dosage.

Conclusion

Many studies demonstrated the relationship between imatinib plasma trough level and efficacy in GIST treatment with a threshold of 1100ng/ml. Imatinib plasma level can be altered by several factors including food intake, albumin and AGP levels, and genetic polymorphism of cytochrome P450. Moreover, it cannot be clinically predicted, which thus justifies measuring TDM to verify that the patient has a plasma concentration within the therapeutic range before increasing dosage or prematurely conclude to ineffectiveness of imatinib.