Genetic testing for UGT1A1*28 and *6 in Japanese patients who receive irinotecan chemotherapy

Akiyama, Yoshitsugu; Fujita, Ken‐ichi; Nagashima, Fumio; Yamamoto, Wataru; Endo, Hisashi; Sunakawa, Yu; Yamashita, Keishi; Ishida, Hiroo; Mizuno, Keiko; Araki, Kazuhiro; Ichikawa, Wataru; Miya, Toshimichi; Narabayashi, Masaru; Kawara, Kaori; Sugiyama, Minako; Hirose, Takashi; Ando, Yumiko; Sasaki, Yasutsuna

doi:10.1093/annonc/mdn645

Cited by 44 publications

(29 citation statements)

References 4 publications

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“…UGT1A1 * 6 , however, is exclusively present in approximately 10-20% of Asians [13,17]. In this study, which only included Korean patients, the allele frequencies of UGT1A1 * 28 and * 6 were 29 and 10%, respectively, which is consistent with a recent Japanese study [21]. The incidence of grade 3-4 diarrhea in clinical trials in the Republic of Korea has been low (1.2-1.7%) in comparison to Western trials (10-22%) [22,23,24,25].…”

Section: Discussionsupporting

confidence: 90%

A Phase I Study of UGT1A1 28/6 Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI

Kim¹,

Hong²,

Lee³

et al. 2014

Oncology

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Purpose: A UGT1A1 genotype-directed dose escalation of irinotecan (CPT-11) was performed in patients with metastatic colorectal cancer receiving first-line FOLFIRI chemotherapy. Methods: Patients were genotyped for UGT1A1 and stratified according to the number of defective alleles (DA; *28 and *6). The irinotecan dose was escalated with a fixed dose of 5-fluorouracil and leucovorin in a standard 3 + 3 design. Results: In 43 enrolled patients, the maximum tolerated dose (MTD) was 300 mg/m² for the 1 DA group, while the MTD was not reached for the 0 DA group with 1 dose-limiting toxicity (DLT) at 330 mg/m² and for the 2 DA group with 0 DLT at 150 mg/m². Because of the risk of being exposed to unsafe doses, the trial was terminated before the MTD was reached in the 0 DA and 2 DA groups. The recommended doses were 300 (0 DA), 270 (1 DA) and 150 (0 DA) mg/m². The 2 DA group displayed 27% lower SN-38 exposure levels relative to the 0 and 1 DA groups (95% CI, 0.47-1.15). Conclusions: The MTD of irinotecan differed according to the UGT1A1 genotype, and higher doses of irinotecan are feasible with sLV5FU2 compared to the present regulatory approved doses. © 2014 S. Karger AG, Basel

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Section: Discussionsupporting

confidence: 90%

A Phase I Study of UGT1A1 28/6 Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI

Kim¹,

Hong²,

Lee³

et al. 2014

Oncology

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“…In colorectal cancer, irinotecan-induced grade 3/4 neutropenia occurs more frequently in patients with the homozygous UGT1A1 * (7)(8)(9). These findings were similar for Japanese patients (9,10) and individuals with low enzyme activity constitute ~10% of the Japanese population (10,11).…”

Section: Introductionsupporting

confidence: 75%

“…In our UGT1A1 polymorphism testing of 134 patients, only 9 patients (6.7%) exhibited low enzyme activity. In the Japanese population, the frequency of individuals with low enzyme activity was reported to be ~10% (11).…”

Section: Discussionmentioning

confidence: 99%

Clinical usefulness of testing for UDP glucuronosyltransferase 1 family, polypeptide A1 polymorphism prior to the inititation of irinotecan-based chemotherapy

Harada

Saito

Karino

et al. 2014

Molecular and Clinical Oncology

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Abstract. An association between UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphisms and irinotecan-induced neutropenia has been previously reported. In this study, we assessed the clinical usefulness of testing for UGT1A1 polymorphisms prior to the initiation of irinotecan-based chemotherapy, as this remains a controversial subject. A total of 136 lung cancer patients who were treated with a combination of nedaplatin and irinotecan as initial chemotherapy were assessed. Following exclusion of patients exhibiting low UGT1A1 enzyme activity, 70 patients were treated after UGT1A1 polymorphism testing (test group) and 66 patients were treated without UGT1A1 polymorphism testing (non-test group). We retrospectively analyzed and compared the adverse events between the test and the non-test groups and observed no reduction in hematological or non-hematological toxicities in the test group compared to that in the non-test group. Of the 9 patients with grade 4 or 5 non-hematological toxicity, 6 patients had febrile neutropenia (FN). All the patients with FN were aged >70 years. The incidence of adverse events was significantly higher among patients aged >70 years compared to that among younger patients. In conclusion, in patients treated with nedaplatin and irinotecan combination chemotherapy, UGT1A1 polymorphism testing prior to the initiation of chemotherapy did not reduce the incidence of adverse events. Therefore, UGT1A1 polymorphism testing alone may not be sufficient to predict the occurrence of severe adverse events and it may be more important to effectively manage adverse events, particularly in elderly patients.

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“…As such, it has been suggested necessary to analyze UGT1A1*6 in addition to UGT1A1*28 to predict irinotecan-related toxicity in Asian patients (Jada et al, 2007). A Japanese prospective study examined the distributions of UGT1A1*28 and UGT1A1*6 (n=300) and showed that the allele (UGT1A1*28 and/or UGT1A1*6), which exists in 10% of Japanese patients, might lead to an increased risk of irinotecan-related neutropenia (Akiyama et al, 2008).…”

Section: Molecular Markers Of Irinotecanmentioning

confidence: 99%

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

Jiang

et al. 2012

J. Zhejiang Univ. Sci. B

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Abstract:Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide. Although we have made steady progress in chemotherapy and targeted therapy, evidence suggests that the majority of patients undergoing drug therapy experience severe, debilitating, and even lethal adverse drug events which considerably outweigh the benefits. The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments. Prognostic and predictive biomarkers have been the subjects of many published papers, but few have been widely incorporated into clinical practice. Here, we want to review recent biomarker data related to colorectal cancer, which may have been ready for clinical use.

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Genetic testing for UGT1A128 and 6 in Japanese patients who receive irinotecan chemotherapy

Cited by 44 publications

References 4 publications

A Phase I Study of <b><i>UGT1A1</i></b> <b><i>28/</i></b><b><i>6</i></b> Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI

A Phase I Study of <b><i>UGT1A1</i></b> <b><i>28/</i></b><b><i>6</i></b> Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI

Clinical usefulness of testing for UDP glucuronosyltransferase 1 family, polypeptide A1 polymorphism prior to the inititation of irinotecan-based chemotherapy

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

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Genetic testing for UGT1A1*28 and *6 in Japanese patients who receive irinotecan chemotherapy

Cited by 44 publications

References 4 publications

A Phase I Study of <b><i>UGT1A1</i></b> *<b><i>28/</i></b>*<b><i>6</i></b> Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI

A Phase I Study of <b><i>UGT1A1</i></b> *<b><i>28/</i></b>*<b><i>6</i></b> Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI

Clinical usefulness of testing for UDP glucuronosyltransferase 1 family, polypeptide A1 polymorphism prior to the inititation of irinotecan-based chemotherapy

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

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Genetic testing for UGT1A128 and 6 in Japanese patients who receive irinotecan chemotherapy

A Phase I Study of <b><i>UGT1A1</i></b> <b><i>28/</i></b><b><i>6</i></b> Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI

A Phase I Study of <b><i>UGT1A1</i></b> <b><i>28/</i></b><b><i>6</i></b> Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI