DPYD-associated toxicity in gastric cancer therapy: Clinical case

Given the high prevalence and mortality from gastric cancer in the global population, interest in the treatment of this disease is growing. The standard treatment for locally advanced gastric cancer is a combined method that includes radical surgery with perioperative polychemotherapy. For gastric cancer with distant metastases and/or a peritoneal carcinomatosis index of more than 7, as well as for the locally advanced stage, polychemotherapy based on fluoropyrimidines (FP) (5-fluorouracil, capecitabine) is used, which are characterized by the frequent development of toxic reactions. Analysis of foreign literature data with presented clinical cases of FP toxicity demonstrated that characteristic adverse events when using FP are diarrhea, nausea/vomiting, mucositis, myelosuppression, neurotoxicity and palmar-plantar syndrome. Approximately 20–30% of patients receiving FP experience severe toxicity, which can lead to death in 1% of cases, with the main cause being a deficiency of the enzyme dihydropyrimidine dihydrogenase, Due to the lack of recommendations for testing mutations and polymorphisms in the DPYD gene for gastric cancer in the Russian Federation, information on the treatment of toxic post-chemotherapy phenomena in individual clinical cases is relevant. Of particular interest is the clinical observation of a forty-three-year-old patient with morphologically verified gastric adenocarcinoma, a peritoneal carcinomatosis index of 7 and the absence of other distant metastases. After three courses of chemotherapy with the inclusion of 5-fluorouracil and oxaliplatin, the patient developed severe hematological, gastrointestinal toxicity, polyneuropathy, and therefore, on a planned basis. A molecular genetic study was performed to determine the genotype of DPYD*2A/13 associated with a high risk of toxicity during chemotherapy. According to the results of the study, a germinal missense mutation NM_000110.4(DPYD): c.2194G>A (p.Val732Ile) was detected in the DPYD gene. The presented analysis of information from scientific sources and the data of our own clinical observation demonstrate the need to assess the status of the DPYD gene in patients subject to FP therapy. The issue of registering an antidote to 5-fluorouracil and capecitabine – uridine triacetate in the Russian Federation also remains open.

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