Hsiang-Lin Tsai1,2, Po-Jung Chen1, Yen-Cheng Chen1,3, Ching-Chun Li1, Tsung-Kun Chang1, Wei-Chih Su1, Tzu-Chieh Yin1,4,5, Ching-Wen Huang1,2, Jaw-Yuan Wang1,2,3,6,7,8. 1. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung. 2. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung. 3. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung. 4. Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung. 5. Department of Surgery, Kaohsiung Municipal Tatung Hospital, Kaohsiung Medical University, Kaohsiung. 6. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung. 7. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung. 8. Ministry of Health and Welfare Pingtung Hospital, Pingtung.
Abstract
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/m2. RESULTS: Six of the seven patients tolerated 120 mg/m2 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/m2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.
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/m2. RESULTS: Six of the seven patients tolerated 120 mg/m2 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/m2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.
Authors: Federico Innocenti; Richard L Schilsky; Jacqueline Ramírez; Linda Janisch; Samir Undevia; Larry K House; Soma Das; Kehua Wu; Michelle Turcich; Robert Marsh; Theodore Karrison; Michael L Maitland; Ravi Salgia; Mark J Ratain Journal: J Clin Oncol Date: 2014-06-23 Impact factor: 44.544
Authors: Janelle M Hoskins; Eugenio Marcuello; Albert Altes; Sharon Marsh; Taylor Maxwell; Derek J Van Booven; Laia Paré; Robert Culverhouse; Howard L McLeod; Montserrat Baiget Journal: Clin Cancer Res Date: 2008-03-15 Impact factor: 12.531
Authors: S Negoro; M Fukuoka; N Masuda; M Takada; Y Kusunoki; K Matsui; N Takifuji; S Kudoh; H Niitani; T Taguchi Journal: J Natl Cancer Inst Date: 1991-08-21 Impact factor: 13.506