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Eur J Cancer. 2016 Apr;57:31-8. doi: 10.1016/j.ejca.2015.12.029. Epub 2016 Feb 4.

Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting.

Author information

1
Univ. de Bordeaux, Bordeaux, F-33000, France; INSERM, U1219, Bordeaux, F-33000, France; CHU de Bordeaux, Bordeaux, F-33000, France.
2
Univ. de Bordeaux, Bordeaux, F-33000, France.
3
Univ. de Bordeaux, Bordeaux, F-33000, France; INSERM CIC Bordeaux CIC1401 Pharmaco-épidemiologie, Bordeaux, F-33000, France.
4
Institut Bergonié, Bordeaux, F-33000, France.
5
Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, F-31300, France.
6
Centre René Gauducheau, Nantes (Saint-Herblain), F-44805, France.
7
Institut de Cancérologie Lucien Neuwirth, Saint Priest-en-Jarez, F-42270, France.
8
CHU La Timone, Marseille, F-13385, France; Aix Marseille Université (AMU), France.
9
Institut de Cancérologie de Lorraine - Alexis Vautrin, Nancy, F-54500, France.
10
Centre Val d'Aurelle, Montpellier, F-34298, France.
11
Centre Oscar Lambret, Lille, F-59020, France.
12
Centre Léon Bérard, Lyon, F-69008, France; Université Claude Bernard Lyon 1, France.
13
CHU Robert Debré, Reims, F-51092, France.
14
Institut Gustave-Roussy, Villejuif, F-94805, France.
15
Univ. de Bordeaux, Bordeaux, F-33000, France; INSERM, U1219, Bordeaux, F-33000, France; CHU de Bordeaux, Bordeaux, F-33000, France. Electronic address: mathieu.molimard@u-bordeaux.fr.

Abstract

BACKGROUND:

Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST.

PATIENTS AND METHODS:

Advanced GIST patients (n=96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively.

RESULTS:

Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p=0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p=0.0256) and for both stomach (p=0.043) and small bowel (p=0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p=0.0271) in the whole population independently of the anatomical localisation.

CONCLUSION:

Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.

KEYWORDS:

Gastrointestinal stromal tumour; Imatinib; Therapeutic drug monitoring

PMID:
26851399
DOI:
10.1016/j.ejca.2015.12.029
[Indexed for MEDLINE]

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