| Autor: |
Masashi, Takano, Kaichiro, Yamamoto, Tsutomu, Tabata, Yuji, Minegishi, Takuma, Yokoyama, Eiji, Hirata, Takeshi, Ikeda, Muneaki, Shimada, Kouzo, Yamada, Satoshi, Morita, Yuichi, Ando, Koji, Hirata, Masahiro, Sugihara, Toru, Sugiyama, Yasuo, Ohashi, Yuh, Sakata |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Asia-Pacific journal of clinical oncology. 12(2) |
| ISSN: |
1743-7563 |
| Popis: |
Irinotecan-induced severe toxicities are possibly related to UGT1A1*6 and *28 genotypes. However, the correlation between UGT1A1 polymorphisms and the risk of toxicities induced by low-dose irinotecan plus platinum combination therapy still remains controversial. This prospective observational study aimed to examine the correlation between UGT1A1 genotypes and clinical outcomes of low-dose irinotecan (median 60 mg/m(2) , range 25-115 mg/m(2) ) plus platinum in Japanese patients with solid tumors.Toxicity profiles were compared between UGT1A1 SNP heterozygotes (hetero-group) and patients with homozygous SNP profile (*6/*6, *28/*28 and *6/*28). Logistic regression models were used to identify independent risk factors for these toxicities.A total of 331 patients were enrolled: 84% with hetero-group and 16% with homo-group. Although the initial irinotecan dose was similar, the dose intensities during the three cycles were significantly lower in the homo-group (P0.01). Grade 3/4 hematological toxicities were significantly more frequent in the homo-group. Multivariable analysis identified UGT1A1 genotype (P0.01) as an independent factor for grade 4 hematological toxicity in the first treatment cycle.UGT1A1 genotype has a major impact on the increased risk of severe hematological toxicities, even in low-dose irinotecan regimens. UGT1A1 genotypes are useful biomarkers for predicting severe hematological toxicities in patients treated with irinotecan plus platinum analog. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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