FDA Calls for Testing Before Treatment With Widely Used Chemotherapies

 Oncology specialists should inform patients about a risk of serious toxicity related to dihydropyrimidine dehydrogenase (DPD) deficiency and should test for DPYD variants before starting treatment with capecitabine (Xeloda) and fluorouracil, the FDA announced.

In a safety update communication, the agency noted that DPYD encodes DPD, which breaks down more than 80% of fluorouracil. Certain homozygous or compound heterozygous DPYD variants result in complete or near-complete absence of DPD activity, increasing the risk for serious, potentially fatal toxicities when exposed to capecitabine or fluorouracil, which are widely used in cancer treatment. Potential adverse reactions include mucositis, diarrhea, neutropenia, and neurotoxicity. The reactions also can occur in patients who have partial DPD activity.

Capecitabine and fluorouracil, or 5-FU, are routinely used in treatment regimens for breast, colorectal, gastric, and pancreatic cancers.

The update adds to previously approved labeling revisions, incorporating more information on DPD deficiency. The revisions include a boxed warning about potentially serious adverse reactions and deaths in patients with complete DPD deficiency. Oncologists are advised to test patients for DPYD variants prior to initiating treatment with the drugs, unless immediate treatment is necessary. 

A new subsection of the product labels' dosing and administration section advises oncologists to avoid capecitabine and fluorouracil in patients who have variants that result in complete DPD deficiency. Dosing should be individualized for patients with partial DPD deficiency.

An estimated 2 million patients worldwide receive the fluoropyrimidines capecitabine and fluorouracil each year. Though widely used, the drugs have a narrow therapeutic index, as 30-40% of patients treated with the drugs develop grade ≥3 toxicity, and up to 1% of adverse reactions prove to be fatal.

https://www.medpagetoday.com/hematologyoncology/othercancers/119774