Irinotecan dose reduction in metastatic colorectal cancer patients with homozygous polymorphism: a single-center case series

Autor: Hsiang-Lin Tsai, Po-Jung Chen, Yen-Cheng Chen, Ching-Chun Li, Tsung-Kun Chang, Wei-Chih Su, Tzu-Chieh Yin, Ching-Wen Huang, Jaw-Yuan Wang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of International Medical Research, Vol 50 (2022)
Druh dokumentu: article
ISSN: 1473-2300
03000605
DOI: 10.1177/03000605221110697
Popis: Objective The UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the UGT1A1*28 polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy. Methods We analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for UGT1A1*28 and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m 2 . Results Six of the seven patients tolerated 120 mg/m 2 irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed. Conclusions mCRC patients homozygous for the UGT1A1*28 allele can tolerate irinotecan at an initial dose of 120 mg/m 2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.
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