DPYD and UGT1A1 genotyping to predict adverse events during first-line FOLFIRI or FOLFOXIRI plus bevacizumab in metastatic colorectal cancer

Abstract

Our study addresses the issue of the clinical reliability of three candidate DPYD and one UGT single nucleotide polymorphisms in predicting 5-fluorouracil- and irinotecan-related adverse events. To this purpose, we took advantage of a large cohort of metastatic colorectal cancer patients treated with first-line 5-fluorouracil- and irinotecan-based chemotherapy regimens (i.e., FOLFIRI or FOLFOXIRI) plus bevacizumab in the randomized clinical trial TRIBE by GONO (clinicaltrials.gov: NCT00719797), in which adverse events were carefully and prospectively collected at each treatment cycle. Here we show that patients bearing DPYD c.1905+1G/A and c.2846A/T genotypes, together with UGT1A1*28 variant carriers, have an increased risk of experiencing clinically relevant toxicities, including hematological AEs and stomatitis. No carrier of the DPYD c.1679T>G minor allele was identified. Present results support the preemptive screening of mentioned DPYD and UGT1A1 variants to identify patients at risk of clinically relevant 5-fluoruracil- and irinotecan-related AEs, in order to improve treatments’ safety through a “genotype-guided” approach.

Implementing a multidisciplinary approach for older adults with Cancer: geriatric oncology in practice

“…As cancer survivors live longer, evaluating long-term adverse effects is imperative [47]. These include physical and psychological issues including, fatigue, pain, osteoporosis, cardiac toxicity, weight and nutritional changes, cognitive changes, depression, anxiety, and neuropathy, among others [48]. Furthermore diminished social and economic resources may also impact the survivorship experience [49].…”

Implementing a Multidisciplinary Approach for Older Adults with Cancer: Geriatric Oncology in Practice

“…42 These include physical and psychological issues including, fatigue, pain, osteoporosis, cardiac toxicity, weight and nutritional changes, cognitive changes, depression, anxiety, and neuropathy, among others. 43 Furthermore diminished social and economic resources may also impact the survivorship experience. 44 This myriad of unmet needs and complexities, coupled with the reduction in services available for older cancer survivors post-treatment, warrant a more robust provision of survivorship follow-up care.…”

Implementing a Multidisciplinary Approach for Older Adults with Cancer: Geriatric Oncology in Practice

“…41 These include physical and psychological issues including, fatigue, pain, osteoporosis, cardiac toxicity, weight and nutritional changes, cognitive changes, depression, anxiety, and neuropathy, among others. 42 Furthermore diminished social and economic resources may also impact the survivorship experience. 43 This myriad of unmet needs and complexities, coupled with the reduction in services available for older cancer survivors post-treatment, warrant a more robust provision of survivorship follow-up care.…”