We present a case of a 48-year-old Caucasian man, compound heterozygous variant carrier of the DPYD gene (HapB3 and c.2194G>A) who had a diagnosis of adenocarcinoma of the left colon and was safely treated with a pharmacogenetic-guided 25% dose reduction of the standard CAP adjuvant treatment. Compound heterozygosis may have been responsible for an earlier over exposure to CAP resulting into low-grade toxicity with an anticipated median time to toxicity of the c.2194G>A variant to the 4th vs. 6th cycles. Some haplotypes of DPYD variants may have an advantage in terms of survival compared to wild-type patients. Our patient may also have benefitted from compound heterozygosis, as shown by no evidence of disease (NED) at 6-month follow-up.
Pharmacogenetic-guided dosing of DPYD intermediate metabolizer compound heterozygous HapB3 and c.2194G>A variant carries should be managed by a multidisciplinary team with a dose reduction ranging from 25 to 50% to maintain effectiveness and close clinical monitoring for early detection of ADRs.
方法:我们介绍了一个48岁的白种人,DPYD基因的复合杂合变体携带者(HapB3和c.2194G>A),诊断为左结肠腺癌,并通过药物遗传学指导的剂量减少25%的标准CAP辅助治疗安全治疗。复合杂合可能是导致早期过度暴露于CAP的原因,导致低度毒性,预期的中位毒性时间为c.2194G>A变体至第4与第六周期与野生型患者相比,DPYD变体的一些单倍型可能在存活方面具有优势。我们的病人也可能从复合杂合中受益,如6个月随访时无疾病证据(NED)所示。
结论:药物遗传学指导剂量的DPYD中间代谢物复合杂合子HapB3和c.2194G>变种携带者应由多学科团队管理,剂量减少25%至50%,以保持有效性并密切临床监测,以早期发现ADR。