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, Midori Shimada, Takeshi Kitazaki, Seiji Nagashima, Kohji Hashiguchi, Noriyuki Ebi, Koichi Takayama, Yoichi Nakanishi, Hiroshi Semba, Taishi Harada, Takashi Seto, Isamu Okamoto, Yukito Ichinose, Kenji Sugio

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)40-45
Number of pages6
JournalThoracic Cancer
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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irinotecan
Lung Neoplasms
Lung
Maximum Tolerated Dose
Glucuronosyltransferase
Leukopenia

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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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). / Fukuda, Minoru; Shimada, Midori; Kitazaki, Takeshi; Nagashima, Seiji; Hashiguchi, Kohji; Ebi, Noriyuki; Takayama, Koichi; Nakanishi, Yoichi; Semba, Hiroshi; Harada, Taishi; Seto, Takashi; Okamoto, Isamu; Ichinose, Yukito; Sugio, Kenji.

In: Thoracic Cancer, Vol. 8, No. 1, 01.01.2017, p. 40-45.

Research output: Contribution to journalArticle

Fukuda, M, Shimada, M, Kitazaki, T, Nagashima, S, Hashiguchi, K, Ebi, N, Takayama, K, Nakanishi, Y, Semba, H, Harada, T, Seto, T, Okamoto, I, Ichinose, Y & Sugio, K 2017, '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)', Thoracic Cancer, vol. 8, no. 1, pp. 40-45. https://doi.org/10.1111/1759-7714.12407
Fukuda, Minoru ; Shimada, Midori ; Kitazaki, Takeshi ; Nagashima, Seiji ; Hashiguchi, Kohji ; Ebi, Noriyuki ; Takayama, Koichi ; Nakanishi, Yoichi ; Semba, Hiroshi ; Harada, Taishi ; Seto, Takashi ; Okamoto, Isamu ; Ichinose, Yukito ; Sugio, Kenji. / 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). In: Thoracic Cancer. 2017 ; Vol. 8, No. 1. pp. 40-45.
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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.",
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T1 - Phase I study of irinotecan for previously treated lung cancer patients with the UGT1A1*28 or *6 polymorphism

T2 - Results of the Lung Oncology Group in Kyushu (LOGIK1004A)

AU - Fukuda, Minoru

AU - Shimada, Midori

AU - Kitazaki, Takeshi

AU - Nagashima, Seiji

AU - Hashiguchi, Kohji

AU - Ebi, Noriyuki

AU - Takayama, Koichi

AU - Nakanishi, Yoichi

AU - Semba, Hiroshi

AU - Harada, Taishi

AU - Seto, Takashi

AU - Okamoto, Isamu

AU - Ichinose, Yukito

AU - Sugio, Kenji

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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