Saito Yoshitaka, Takekuma Yoh, Komatsu Yoshito, Sugawara Mitsuru
Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.
Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
J Oncol Pharm Pract. 2021 Jun;27(4):1020-1025. doi: 10.1177/1078155220956691. Epub 2020 Sep 16.
S-1, a compounding agent of tegafur, gimeracil, and oteracil potassium, is one of the most effective chemotherapeutic agents for colorectal cancer. In this case, following S-1 administration, we observed predominant elevation of serum triglyceride.
A 49-year-old man with stage IV transverse colon adenocarcinoma received S-1 + irinotecan + bevacizumab. At the end of the S-1 administration period in every course, his serum triglyceride level was found to be elevated. Finally, it reached grade 4, without any symptoms of acute pancreatitis in the fifth course, and fenofibrate 80 mg once a day was administered. Interestingly, the elevation spontaneously normalized without any pharmacotherapy 14 days after S-1 withdrawal, and this elevation did not occur when S-1 was not administered. Further, fenofibrate administration attenuated the hypertriglyceridemia to grades 1-3, with no complications.
S-1 administration induced hypertriglyceridemia owing to the elevated serum triglyceride; however, a contrasting result was observed in the S-1 withdrawal period and during the S-1-cessation cycle. Since dietary intake was poorer during the S-1 administration period, it is considered that S-1 might have disturbed lipid metabolism. Further, we know that capecitabine, which is a prodrug of fluorouracil, also induces hypertriglyceridemia. As the end product of these medicines is fluorouracil, the presence of fluorouracil or its metabolizing enzymes, the genetic background of the patient might have affected the results. We have to be aware of the risk of asymptomatic and temporal occurrence of hypertriglyceridemia by S-1 administration for the early detection with appropriate pre-emptive treatment.
替吉奥（S-1）是替加氟、吉美嘧啶和奥替拉西钾的复方制剂，是治疗结直肠癌最有效的化疗药物之一。在本病例中，服用S-1后，我们观察到血清甘油三酯显著升高。
一名49岁的IV期横结肠癌男性患者接受了S-1+伊立替康+贝伐单抗治疗。在每个疗程的S-1给药期结束时，发现他的血清甘油三酯水平升高。最终，在第五个疗程中达到4级，且无急性胰腺炎的任何症状，于是每天给予80毫克非诺贝特。有趣的是，停用S-1后14天，甘油三酯升高未经任何药物治疗便自行恢复正常，且未服用S-1时未出现这种升高情况。此外，服用非诺贝特可将高甘油三酯血症减轻至1-3级，且无并发症。
服用S-1导致血清甘油三酯升高从而引起高甘油三酯血症；然而，在停用S-1期间和S-1停药周期观察到了相反的结果。由于在S-1给药期间饮食摄入较差，因此认为S-1可能干扰了脂质代谢。此外，我们知道氟尿嘧啶的前体药物卡培他滨也会引起高甘油三酯血症。由于这些药物的最终产物是氟尿嘧啶，氟尿嘧啶或其代谢酶的存在、患者的遗传背景可能影响了结果。我们必须意识到服用S-1会有无症状且短暂发生高甘油三酯血症的风险，以便通过适当的预防性治疗进行早期检测。
