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. 2017 Jan;8(1):40-45.
doi: 10.1111/1759-7714.12407. Epub 2016 Nov 24.

Phase I study of irinotecan for previously treated lung cancer patients with the UGT1A1*28 or *6 polymorphism: Results of the Lung Oncology Group in Kyushu (LOGIK1004A)

Minoru Fukuda  1 , Midori Shimada  2 , Takeshi Kitazaki  2 , Seiji Nagashima  3 , Kohji Hashiguchi  2 , Noriyuki Ebi  4 , Koichi Takayama  5 , Yoichi Nakanishi  6 , Hiroshi Semba  7 , Taishi Harada  6 , Takashi Seto  8 , Isamu Okamoto  6 , Yukito Ichinose  9 , Kenji Sugio  10   11
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Phase I study of irinotecan for previously treated lung cancer patients with the UGT1A1*28 or *6 polymorphism: Results of the Lung Oncology Group in Kyushu (LOGIK1004A)

Minoru Fukuda et al. Thorac Cancer. 2017 Jan.

Abstract

Background: Various polymorphisms have been detected in the UDP-glucuronosyltransferase 1A ( UGT1A ) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism.

Methods: The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /- and *6 /-), were aged ≤75 years old, had a performance score of 0-1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36.

Results: Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2 , but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment.

Conclusions: The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2 .

Keywords: UGT1A 1; Gene polymorphism; irinotecan; lung cancer; phase I.

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