科研之友
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摘要
BACKGROUND: Infusional fluorouracil/leucovorin (FU/LV) plus irinotecan (FOLFIRI) is one of the standard first-line options for patients with metastatic colorectal cancer (mCRC). Irinotecan is converted into 7-ethyl-10-hydroxycamptothecin (SN-38) by a carboxylsterase and metabolised through uridine diphosphate glucuronosyl transferase (UGT1A1). The UGT1A1*28 allele has been associated with the risk of developing severe toxicities. The present trial was designed to define the maximum tolerated dose according to UGT1A1 genotype. This report focuses on the results of tolerance to different escalated doses of FOLFIRI first-line of chemotherapy.
PATIENTS AND METHODS: Patients undergoing first-line treatment for mCRC and eligible for treatment with FOLFIRI were classified according to UGT1A1 genotype. A total of 94 patients were eligible for dose escalation of irinotecan. The starting dose of biweekly irinotecan was 180 mgm(-2) for the *11, 110 mgm(-2) for the *128 and 90 mgm(-2) for the *2828 genotypes. RESULTS: The dose of irinotecan was escalated to 450 mgm(-2) in patients with the *11 genotype, to 390 mgm(-2) in those with the *128 genotype and to 150 mgm(-2) in those with the *2828 genotype. Neutropenia and diarrhoea were the most common grade 3 or 4 toxicities.
CONCLUSIONS: Our results demonstrated that the recommended dose of 180 mgm(-2) for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated for patients with the UGT1A1 *11 and *128 genotypes. The maximum tolerable dose (MTD) in patients with a high-risk UGT1A1 *2828 genotype is 30% lower than the standard dose of 180 mgm(-2). British Journal of Cancer (2011) 105, 53-57. doi:10.1038/bjc.2011.206 www.bjcancer.
- 出版日期2011-6-28
