| Autor: |
Cassandra White, Hannah Wardill, Christine Paul, Timothy Price, Christos Karapetis, Mark Nalder, Matthew E. Burge, Ann Thomas, Chris Oldmeadow, Daniel Barker, Laura C. Edney, Janet Coller, Joanne Bowen, Cheri Ostroff, Bruce Cheek, Mel Carlson, Trumaine Rankmore, Adnan Nagrial, Stephen Clarke, Lorraine Chantrill, Stephen Ackland, Rodney J. Scott |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
BMC Cancer, Vol 24, Iss 1, Pp 1-10 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2407 |
| DOI: |
10.1186/s12885-024-13122-8 |
| Popis: |
Abstract Background Fluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3–4 (≥ G3) toxicities that require hospital-based management ± intensive care admission. Approximately 1% of patients die secondary to FP toxicities. Prospective screening for DPYD gene variants (encoding the key enzyme for FP catabolism) can identify patients at risk of ≥ G3 toxicity and allow for dose adjustment prior to first FP exposure. Evidence supports this as a cost-effective method of improving patient safety and reducing healthcare burden internationally; however, no Australian data confirms its feasibility on a large scale. Method This investigator-led, single-arm study will determine large scale feasibility of prospective DPYD genotyping, confirming patient safety and cost-effectiveness within the Australian health care system. 5000 patients aged 18 years and older with solid organ cancers requiring FP chemotherapy will be consented and genotyped prior to commencing treatment, and early toxicity (within 60 days) post-FP exposure will be determined. Toxicity data for DPYD variant carriers who have dose adjustments will be compared to the wild-type cohort and historical cohorts of carriers who did not undergo genotyping prior to FP exposure, and prospective variant carriers who do not undergo dose-adjustment. Prevalence of the four standard DPYD gene variants will be confirmed in an Australian population. Additionally, health economic analysis, implementation research via semi-structured interviews of patients and clinicians, and feasibility of UGT1A1 genotyping will be conducted. Discussion This study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing. Trial registration This trial was registered with the Australian and New Zealand Cancer Trials Registry on 13th Dec 2023, ACTRN12623001301651. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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