An enzyme deficiency, which is not so rare, is thought to be responsible for 10 to 40% of severe acute toxicities during chemotherapy with 5-FU salts. A diagnostic test is now recommended.
Certain chemotherapies used in approximately 60% of anticancer treatments (breast, ENT, colon and rectum), are believed to be the cause of nearly 200 patient deaths each year in France.
These are polychemotherapies based on fluoropyrimidines, that is to say 5-FU, its derivative salts and its prodrug, capecitabine when they are administered without dose adjustment to patients who have a total deficit in “DPD” (dihydropyrimidine dehydrogenase), the enzyme that is naturally responsible for the elimination of fluoropyrimidines from the body.
Severe toxicities and treatment delays
In addition, these 5-FU-based chemotherapies induce severe toxicities in 10 to 40% of patients. These severe toxicities are disabling enough to require hospitalization: decrease in the number of blood cells such as anemia or leukopenia, diarrhea, vomiting, dehydration or even coma.
When they are not severe enough to lead to hospitalization, 5-FU toxicities are nevertheless responsible for a disruption of the normal therapeutic protocol with subsequent delays in treatment and under-dosing which impairs efficacy.
A deficit not so rare but unpredictable
It is estimated that between 3 and 10% of cancer patients have a partial DPD deficiency and between 0.1 and 0.5% a total DPD deficiency, which makes them partially or totally intolerant to 5-FU. For these people, who have no risk factors, the use of these molecules at a standard dose can be the cause of many toxicities, severe or even fatal.
If this deficit is ignored, prescribing 5-FU at a normal dose to all patients amounts to “playing Russian roulette”, because even if antagonists exist, they must be started within 96 hours. the onset of toxicity.
A multiparametric diagnostic test
Different diagnostic methods exist, but they each have their shortcomings: 84% diagnostic for phenotypic tests and 33% for genotypic tests.
Thus, only the multiparametric tests, that is to say combining the 2 methods, can find 100% of enzymatic deficits and thus allow these treatments to be administered at the right dose.
The price problem
A ANSM administrative circular makes it almost compulsory to screen for a DPD deficiency in these circumstances, in order to avoid the toxicities that may arise, the problem is that the reimbursement of this test (190 Euros) is not addressed.
If this expense during chemotherapy carried out in hospital can be covered in the hospital package, with a reduction in the resources of hospitals and clinics in a period when deficits are frequent, reimbursement is not provided for in the context of ” outpatient treatment.
A probable blocking element for the perfect application of this yet essential screening.
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