{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T20:58:49Z","timestamp":1763585929896,"version":"3.45.0"},"reference-count":15,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"11","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Glob Oncol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Dihydropyrimidine dehydrogenase (DPD) deficiency, an autosomal recessive metabolic disorder, causes a considerable deficit in the patient's metabolism of fluoropyrimidine drugs, most notably 5-fluorouracil (5-FU) and capecitabine. There is a higher frequency of severe toxicities after a fluoropyrimidine regimen among patients with GI and hepatopancreaticobiliary (HPB) malignancies on chemotherapy because of this metabolic deficiency. This prospective study aims to assess the rate of DPD deficiency and clinical significance of DPD deficiency in patients receiving fluoropyrimidine chemotherapy at a tertiary oncology center in India.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>From March 2024 to February 2025, we prospectively recruited 146 patients with histologic confirmation of GI and HPB cancers who were commencing a 5-FU\u2013 or capecitabine-based regimen. We performed pretreatment DPD tests on all patients using TRUPCR DPYD reverse transcriptase polymerase chain reaction for four known variants. Severe toxicities (Common Terminology Criteria for Adverse Events v5.0) were assessed after the first cycle of chemotherapy. Dose reductions, advances in therapy, and admissions were also noted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Of the 146 study participants, 11 (7.5%) had a DPYD mutation. HapB3 (rs56038477) was the most commonly encountered variant (72.7% of patients), along with registries of DPYD*2A (18.2%) mutation and mutation c.2846A&gt;T (9.1%). Severe toxicities (grade \u22653) were above other grade toxicities (61.6%) in mutation carriers (72.7%) as compared with mutation noncarriers (37.0%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .03). Neutropenia, diarrhea, and thrombocytopenia were the common toxicities at a frequency of 18.5%, 12.3%, and 15.1%, respectively. After dose reduction, 90.9% of mutation carriers required a dose reduction versus 14.8% of mutation noncarriers (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). Both groups had no problems in completing treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Individuals with DPYD mutations experience increased toxicity and dose adjustments; however, treatment efficacy was not affected. This indicates that a coordinated effort that incorporates routine DPYD testing can mitigate treatment toxicities and individualized fluoropyrimidine dosing for patients with GI and HPB cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/go-25-00442","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T20:57:16Z","timestamp":1763585836000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Implications of Dihydropyrimidine Dehydrogenase Deficiency in GI and Hepatopancreaticobiliary Cancers Treated With Fluoropyrimidines: A Prospective Observational Study"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3590-3261","authenticated-orcid":true,"given":"Varun","family":"Goel","sequence":"first","affiliation":[{"name":"Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1602-0543","authenticated-orcid":true,"given":"Dharmishtha Ashis","family":"Basu","sequence":"additional","affiliation":[{"name":"Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3916-4411","authenticated-orcid":true,"given":"Arpit","family":"Jain","sequence":"additional","affiliation":[{"name":"Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9770-1246","authenticated-orcid":true,"given":"Nivedita","family":"Patnaik","sequence":"additional","affiliation":[{"name":"BLK-Max Super Speciality Hospital, Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akanksha","family":"Jaju","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Hospital, Pitampura, Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6517-3664","authenticated-orcid":true,"given":"Anurag","family":"Mehta","sequence":"additional","affiliation":[{"name":"Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9149-6969","authenticated-orcid":true,"given":"Vineet","family":"Talwar","sequence":"additional","affiliation":[{"name":"Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113308"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.11.2248"},{"key":"e_1_3_5_4_2","first-page":"181","article-title":"dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration","volume":"4","author":"Ezzeldin H","year":"2004","unstructured":"Ezzeldin H, Diasio R: dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. 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Eur J Cancer 164:153-164, 2022","journal-title":"Eur J Cancer"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.97686"},{"key":"e_1_3_5_14_2","first-page":"547","article-title":"Pharmacogenetics and metabolism from science to implementation in clinical practice: The example of dihydropyrimidine dehydrogenase","volume":"23","author":"Del Re M","year":"2017","unstructured":"Del Re M, Restante G, Di Paolo A, et al: Pharmacogenetics and metabolism from science to implementation in clinical practice: The example of dihydropyrimidine dehydrogenase. Curr Pharm Des 23:547-556, 2017","journal-title":"Curr Pharm Des"},{"key":"e_1_3_5_15_2","first-page":"A4842","article-title":"Prevention of severe toxicity from capecitabine, 5-fluorouracil and tegafur by screening for DPD-deficiency","volume":"156","author":"Deenen MJ","year":"2012","unstructured":"Deenen MJ, Meulendijks D, Cats A, et al: Prevention of severe toxicity from capecitabine, 5-fluorouracil and tegafur by screening for DPD-deficiency. Ned Tijdschr Geneeskd 156:A4842, 2012","journal-title":"Ned Tijdschr Geneeskd"},{"key":"e_1_3_5_16_2","first-page":"61","article-title":"Profiling dihydropyrimidine dehydrogenase deficiency in patients with cancer undergoing 5-fluorouracil\/capecitabine therapy","volume":"6","author":"Mercier C","year":"2006","unstructured":"Mercier C, Ciccolini J, Serdjebi C, et al: Profiling dihydropyrimidine dehydrogenase deficiency in patients with cancer undergoing 5-fluorouracil\/capecitabine therapy. 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