L'équipe du département de pharmacologie

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Université Bordeaux 2 CHU de Bordeaux INSERM
Département Hospitalo-Universitaire de Pharmacologie de Bordeaux
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Imatinib study and monitoring

 


 

Imatinib treatment

The first anticancer drug of the tyrosine kinase inhibitor family, imatinib mesylate (Glivec®, or Gleevec®) has become the treatment of choice for first-line treatment of Chronic Myeloid Leukemia (CML) owing to its efficacy and good tolerance.

It is currently also prescribed for the treatment of certain gastrointestinal stromal tumours (GIST): standard treatment for inoperable and/or metastatic locally advanced GIST [1], it was approved by the European Commission in May 2009 for adjuvant treatment in patients with a significant risk of relapse after tumour resection [2].

 


 

Therapeutic window

The therapeutic effect of imatinib depends on its plasma concentration and a therapeutic drug monitoring allows the physician to adapt the dose and to optimise the efficacy of treatment for his or her patient. In 2007 the the pharmacotoxicology laboratory initiated the creation of a therapeutic drug monitoring database in order to define the therapeutic window of imatinib in the treatment of CML and GIST. This study, promoted by the teaching hospitals of Bordeaux, is directed by Pr. M. Molimard.

 


 

Progress report - February 2010

Imatinib blood level testing (trough plasma level determination)

At the 8th of February 2010, 6029 dosings have been performed for the therapeutic drug monitoring of 3445 patients of 24 European countries. The principal indication was CML (86% of patients, and 81% of the tests performed), followed by GIST (8% of patients, and 12% of tests performed). Several samples (5% of tests) were also performed for the monitoring of certain forms of Philadelphia chromosome-positive Acute lymphocytic leukemia (Phi+ ALL), Graft versus host diseases (GVH), and certain malignant or benign dermatological conditions (dermatosarcoma or sclerodermatitis).

 

Imatinib tests performed (for identified pathologies)
Pathologies Dosings performed Patients
CML 4905 2973
Phi + ALL 261 106
GVH 31 15
Dermatosarcoma or Sclerodermatitis 45 26
GIST 735 287
     

 

Dissemination of the method

In the context of the EUTOS programme, the pharamcotoxicology laboratory has been designated by Novartis as the European centre of reference and expertise for imatinib plasma level determination in the therapeutic drug monitoring of patients with CML. At the time of writing we have started the dissemination of the methodology to the pharmacology laboratories of hospitals across Europe. We have undertaken the diffusion of the method for dose determination to other pharmacology laboratories and at the time of writing the method has been validated in 35 laboratories across Europe.

 

Data analysis
The results of the analysis in December 2009 confirm the minimal effective concentration of 1000 ng/mL for CML with a more favourable probability of cytogenetic and molecular response above this threshold.
We are currently developing the study of therapeutic monitoring of GIST with the objective of determining the minimal effective concentration that allows the increase of progression-free survival. Incidentally, a recent study conducted on locally advanced inoperable and/or metastatic GIST has found a better response in patients with plasma concentrations above 1100 ng/mL [3].
To continue the implementation of the database, we invite you to fill-out the monitoring request form each time a sample is sent.

 

Newsletters

Updates on study progress are available from the GIST or LMC newsletters.

 


 

Monitoring request

Physicians who would like their patients to benefit from the centralised imatinib monitoring offered in the context of the study should send the blood samples collected following the protocol. These samples are to be sent with a monitoring request form for the pathology treated filled-out by the physician.

The 2009 versions in French and English of these forms may be downloaded from this website:

 

For any further information: imatinib@chu-bordeaux.fr

 

 

 

 


References

  1. Casali P G et al., Ann Onc, May 2009; 20: iv64 - iv67
  2. DeMatteo R et al.,The Lancet, 2009, 373: 1097-1104
  3. Demettri G. D. et al J Clin Oncol 27, 2009: 3141-3147