Open Access

ARTICLE

Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated According to Uridine Diphosphate Glucuronosyltransferase 1A1 Genotyping in Patients With Metastatic Colorectal Cancer

Cheng-Jen Ma^*†‡, Ching-Wen Huang^*‡§, Yung-Sung Yeh^*†¶, Hsiang-Lin Tsai^*§#**, Huang-Ming Hu^††‡‡, I-Chen Wu^††‡‡, Tian-Lu Cheng^§§¶¶, Jaw-Yuan Wang^{*†‡§**¶¶}

* Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
† Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
‡ Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
§ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
¶ Division of Trauma and Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
# Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
** Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
†† Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
‡‡ Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
§§ Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
¶¶ Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan

Oncology Research 2017, 25(5), 673-679. https://doi.org/10.3727/97818823455816X14786040691928

Abstract

We analyzed the results of previously treated patients with metastatic colorectal cancer (mCRC) who received regorafenib plus FOLFIRI with the irinotecan dose escalation on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping. Thirteen patients with previously treated mCRC were subjected to UGT1A1 genotyping between October 2013 and June 2015 and were administered regorafenib plus FOLFIRI with irinotecan dose escalation. Patients with UGT1A1*1/*1 and *1/*28 genotypes were administered 180 mg/m² of irinotecan, whereas those with the UGT1A1*28/*28 genotype were administered 120 mg/m2 of irinotecan. For all patients, the irinotecan dose was increased by 30 mg/m2 every two cycles until grade ≥3 adverse events or severe adverse events developed, following which the dose was reverted to and maintained at the previously tolerated level. The oral regorafenib dose was adjusted to 120 mg/day daily. The median follow-up period was 10.0 months (1.0–21.0 months). The disease control rate was 69.2%, whereas the median progression-free survival and overall survival were 9.5 and 13.0 months, respectively. Our findings indicate that regorafenib plus FOLFIRI with irinotecan dose escalation based on UGT1A1 genotyping in previously treated patients with mCRC and with UGT1A1*1/*1 and UGT1A1*1/*28 genotypes is clinically effective and yields improved oncological outcomes.

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