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| Name | Class |
|---|---|
| Ligue contre le cancer, France | OTHER |
| Canceropôle Nord Ouest | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acetylsalicylic acid + loperamide | Experimental | Acetylsalicylic acid + loperamide |
|
| diosmectite + loperamide | Active Comparator | Acetylsalicylic acid + loperamide |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acetylsalicylic acid + loperamide | Drug | In case of inefficiency in one month, according to predefined criteria, acetylsalicylic acid will be stopped and replaced by diosmectite. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy measured by the decrease in the intensity of diarrhea and / or anti-diarrheal consumption | Effectiveness of acetylsalicylic acid versus diosmectite | 1 month |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Three months |
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Inclusion Criteria:
Exclusion Criteria:
Processing acetylsalicylic acid;
Allergy or against-indications to acetylsalicylic acid (including concomitant antiplatelet or anticoagulant considered as increasing the risk of bleeding by the investigator) acid;
Treatment with anti vitamin K or new oral anticoagulants;
Absolute in pursuit of targeted therapy contraindication;
Chronic diarrhea prior to clinical introduction of targeted therapy;
Diarrhoea unrelated to targeted therapy such as:
Grade 3 diarrhea with signs of complications or grade 4
Patients with a history of grade 3 diarrhea with signs of complications or grade 4 during previous treatment with TKI;
Participation in other medical test;
Pregnant women / nursing;
Association with methotrexate at doses > 15 mg / d;
Patient Trust or deprived of liberty.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU | Amiens | France | ||||
| Centre François Baclesse |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| D008139 | Loperamide |
| C033214 | Smectite |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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| diosmectite + loperamide | Drug | In case of inefficiency in one month, according to predefined criteria, diosmectite will be stopped and replaced by acetylsalicylic acid. |
|
| TKI dose reduction |
Proportion of patients requiring dose reduction of targeted therapy |
| Three months |
| Quality of life | Quality of life and its evolution by month using ladders FACIT-G and FACIT-D. | Three months |
| Safety measured by the proportion of adverse event | Safety of acetylsalicylic acid in patients with diarrhea in targeted therapy | Months 1 to 3 |
| Caen |
| 14076 |
| France |
| Centre Hospitalier public du Cotentin | Cherbourg | 50100 | France |
| Centre hospitalier | Compiègne | France |
| Centre Léon Bérard | Lyon | France |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |