The mechanisms of action of the side effects associated with targeted therapies are still poorly understood. He was found in patients treated with gefitinib, increased levels of thromboxane B2 and P-selectin Thromboxane B2 is the result of the hydrolysis of thromboxane A2, which is itself obtained from Prostaglandin H2 under the action of the thromboxane synthetase. The thromboxane A2 is produced by platelets and the active pro-thrombotic properties as follows: stimulation of platelets and activation of other increased platelet aggregation. The selectins are cell adhesion proteins with a role in the adhesion phenomena. P-selectin is expressed by platelets and endothelial cells. The demonstration of increased plasma levels of thromboxane B2 and P-selectin leaves suggest a role of platelet activation in the occurrence of side effects associated with targeted therapies. Kanazawa's study was conducted in 39 Japanese patients, trying to assess the value of low-dose acetylsalicylic acid or 100mg per day, that is to say, anti-aggrégantes doses, the occurrence rash and diarrhea induced by gefitinib. In this study, the group of patients treated with acetylsalicylic acid presented a lower rate of side effects significantly, 58.3% versus 77.8%. The frequency of diarrhea was 18.5% (or 5 patients) in the standard group versus 0% in the group with acetylsalicylic acid. Similarly, it was found a reduction in the occurrence of skin rash, 33.3% or 4 patients in the acetylsalicylic acid group versus 74.1% s, 20 patients in the standard group. Finally, in this study, it was not revealed significant differences in terms of response to treatment with gefitinib (37% in the standard group versus 33% in the group treated with aspirin patient) It does not exist in our knowledge of prospective data evaluating the effect of acetylsalicylic acid on the reduction of side effects associated with targeted in a population of patients of Caucasian-type treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
In case of inefficiency in one month, according to predefined criteria, acetylsalicylic acid will be stopped and replaced by diosmectite.
In case of inefficiency in one month, according to predefined criteria, diosmectite will be stopped and replaced by acetylsalicylic acid.
CHU
Amiens, France
Centre François Baclesse
Caen, France
Centre Hospitalier public du Cotentin
Cherbourg, France
Centre hospitalier
Compiègne, France
Centre Léon Bérard
Lyon, France
Efficacy measured by the decrease in the intensity of diarrhea and / or anti-diarrheal consumption
Effectiveness of acetylsalicylic acid versus diosmectite
Time frame: 1 month
Toxicity
Diarrhea decrease 3 months after the introduction of acetylsalicylic acid or diosmectite; Proportion of patients with a decrease in the grade of diarrhea during the months following the introduction of acetylsalicylic acid or diosmectite. Rate and intensity of side effects associated with other targeted therapy.
Time frame: Three months
TKI dose reduction
Proportion of patients requiring dose reduction of targeted therapy
Time frame: Three months
Quality of life
Quality of life and its evolution by month using ladders FACIT-G and FACIT-D.
Time frame: Three months
Safety measured by the proportion of adverse event
Safety of acetylsalicylic acid in patients with diarrhea in targeted therapy
Time frame: Months 1 to 3
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