Xeloda and 5 FU Toxicity

[ElaineM]

http://www.medscape.com/viewarticle/702737_2
"Do not take XELODA if if you have been told that you don't have enough of the enzyme DPD (dihydropyrimidine dehydrogenase)"
http://www.xeloda.com/about/ (http://www.xeloda.com/about/)



http://en.wikipedia.org/wiki/DPD_deficiency

http://www.healthanddna.com/drug-safety-dna-testing/fluorouracil.html

"5-FU binds to an enzyme inside of cancer cells called Thymidilate Synthetase, and then exerts its anti-cancer effect on the cells. In general, 5-FU is relatively well tolerated at standard doses However, an estimated 3-8% of patients have a genetic variation that leads to a deficiency of an enzyme called Dihydropyrimidine dehydrogenase (DPD) that is crucial for the metabolism and deactivation of 5-FU. Patients with this variation have severe toxic reactions that may be fatal with even small doses and often the very first dose of 5-FU."

I am not trying to scare anyone, but I think this is important enough to share with the her2support members who may be considering Xeloda or who have not had success with Xeloda. I understand the test for this deficiency is a blood test.
Apparently Xeloda and 5 FU need the above enzyme to work properly. If a person does not have enough of the DPD enzyme and takes Xeloda it may not work well or it may cause very toxic side effects.
I wonder how many oncologists test their patients for the deficiency when they are considering Xeloda or 5FU?

[Jackie07]

Here's the abstract of a recent article on the drug (Xeloda = Capecitabine = prodrug of 5 Fu):

http://www.ncbi.nlm.nih.gov/pubmed/20926454

[ElaineM]

Thanks Jackie. I have that one.
Here is more information on the subject from a lab.
http://www.ittlabs.com/dpd.html
5-Fluorouracil was first introduced over 50 years ago, but remains one of the most commonly prescribed chemotherapy drugs as it is used for the treatment of head and neck, breast, skin, gastric, colorectal, and ovarian cancers, among others. Although it is generally well-tolerated, approximately 13-16% of patients that receive 5-FU experience severe toxicity [1, 2]. These 5-FU associated side effects include nausea, vomiting, diarrhea, neutropenia, mucositis, neuropathy, dermatitis, hand-foot syndrome, cardiac toxicity, and, in rare cases, death.
Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolism of 5-FU, and partial or complete deficiency of the DPD enzyme is responsible for the severe side effects in about 40-50% of those patients suffering from severe toxicity [3-5]. Fortunately, for each individual that is scheduled to receive 5-FU based drugs (Adrucil, Efudex, Fluoroplex, Xeloda, or Carac), a DPD enzyme assay can be performed to determine if the individual has normal or deficient DPD activity. If the patient is found to have deficient activity, then he/she could be at risk of severe toxicity when exposed to 5-FU, often with the very first dose. Their physician could be advised of this risk and decide how to proceed with treatment, perhaps by decreasing the patient’s dose or deciding on an alternative treatment option. Fortunately this DPD assay can be performed with minimal involvement from the patient; requiring only a single blood draw.
Who Should Be Tested?
The DPD enzyme assay should be considered for any person who is taking 5-FU based drugs (ie Adrucil, Efudex, Fluoroplex, Xeloda, and Carac) with symptoms of toxicity or anyone being considered for 5-FU based chemotherapy.
Advantages of the DPD Enzyme Deficiency Test
1. Helps to predict those patients that may experience severe 5-FU toxicity before they are ever given the drug.
2. Helps to determine optimal dosing for the patient – if patient is found to be DPD deficient, their dose can be decreased or alternative treatment options could be considered.
3. Requires only a single blood draw from the patient – with quick turn-around time.
4.Useful for all 5-FU based drugs and pro-drugs, including Adrucil, Fluoroplex, Efudex, Xeloda, and Carac.
Click here to find out more and how to order the DPD en