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Erschienen in: Medical Oncology 3/2013

01.09.2013 | Original Paper

Associations between UGT1A1*6/*28 polymorphisms and irinotecan-induced severe toxicity in Chinese gastric or esophageal cancer patients

verfasst von: Jing Gao, Jun Zhou, Yanyan Li, Zhi Peng, Yilin Li, Xicheng Wang, Lin Shen

Erschienen in: Medical Oncology | Ausgabe 3/2013

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Abstract

The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced gastric or esophageal cancer patients. The genotypes of UGT1A1*6 and UGT1A1*28 were analyzed by PCR amplification and Sanger sequencing in 42 gastric and 91 esophageal cancer patients receiving irinotecan-containing chemotherapy. The influences of UGT1A1*6/*28 polymorphisms on severe diarrhea and neutropenia were analyzed. The overall incidence of UGT1A1*6/*28 variants in gastric cancer and esophageal cancer was 38.1 % (GA: 31.0 %; AA: 6.9 %), 28.6 % (TA6/TA7: 26.2 %; TA7/TA7: 2.4 %) and 33.0 % (GA: 28.6 %; AA: 4.4 %), 25.3 % (TA6/TA7: 23.1 %; TA7/TA7: 2.2 %) in our cohort, respectively. A total of 10 patients (gastric cancer: 9.5 %, 4/42; esophageal cancer: 6.6 %, 6/91) had severe diarrhea and 35 patients (gastric cancer: 35.7 %, 15/42; esophageal cancer: 22.0 %, 20/91) had severe neutropenia. Statistic analysis between UGT1A1 genotyping and severe diarrhea was not conducted due to the limited number of patients. For gastric cancer, it seemed that only UGT1A1*6 variant was associated with severe neutropenia (P = 0.042), while among esophageal cancer patients, UGT1A1*6 (P = 0.011) or UGT1A1*28 (P = 0.026) variants were significantly associated with severe neutropenia. UGT1A1*6 variant was closely associated with severe neutropenia both in gastric cancer and in esophageal cancer, but the association between UGT1A1*28 variant and severe neutropenia in gastric and esophageal cancer was not consistent in this study, which would be validated in the future large samples.
Literatur
1.
Zurück zum Zitat Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.PubMedCrossRef Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.PubMedCrossRef
2.
Zurück zum Zitat Ohyanagi F, Horiike A, Okano Y, et al. Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer. Cancer Chemother Pharmacol. 2008;61:503–8.PubMedCrossRef Ohyanagi F, Horiike A, Okano Y, et al. Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer. Cancer Chemother Pharmacol. 2008;61:503–8.PubMedCrossRef
3.
Zurück zum Zitat Yamamoto K, Kokawa K, Umesaki N, et al. Phase I study of combination chemotherapy with irinotecan hydrochloride and nedaplatin for cervical squamous cell carcinoma: Japanese gynecologic oncology group study. Oncol Rep. 2009;21:1005–9.PubMedCrossRef Yamamoto K, Kokawa K, Umesaki N, et al. Phase I study of combination chemotherapy with irinotecan hydrochloride and nedaplatin for cervical squamous cell carcinoma: Japanese gynecologic oncology group study. Oncol Rep. 2009;21:1005–9.PubMedCrossRef
4.
Zurück zum Zitat Takakura S, Takano M, Takahashi F, et al. Randomized phase II trial of paclitaxel plus carboplatin therapy versus irinotecan plus cisplatin therapy as first-line chemotherapy for clear cell adenocarcinoma of the ovary: a JGOG study. Int J Gynecol Cancer. 2010;20:240–7.PubMedCrossRef Takakura S, Takano M, Takahashi F, et al. Randomized phase II trial of paclitaxel plus carboplatin therapy versus irinotecan plus cisplatin therapy as first-line chemotherapy for clear cell adenocarcinoma of the ovary: a JGOG study. Int J Gynecol Cancer. 2010;20:240–7.PubMedCrossRef
5.
Zurück zum Zitat Kaya AO, Coskun U, Gumus M, et al. The efficacy and toxicity of irinotecan with leucovorin and bolus and continuous infusional 5-fluorouracil (FOLFIRI) as salvage therapy for patients with advanced gastric cancer previously treated with platinum and taxane-based chemotherapy regimens. J Chemother. 2012;24(4):217–20.PubMedCrossRef Kaya AO, Coskun U, Gumus M, et al. The efficacy and toxicity of irinotecan with leucovorin and bolus and continuous infusional 5-fluorouracil (FOLFIRI) as salvage therapy for patients with advanced gastric cancer previously treated with platinum and taxane-based chemotherapy regimens. J Chemother. 2012;24(4):217–20.PubMedCrossRef
6.
Zurück zum Zitat Ferte C, Romano O, Mariette C, et al. FOLFIRI chemotherapy in patients with advanced non resectable esophageal or junctional adenocarcinoma: a pilot study. J Chemother. 2011;23(6):358–61.PubMed Ferte C, Romano O, Mariette C, et al. FOLFIRI chemotherapy in patients with advanced non resectable esophageal or junctional adenocarcinoma: a pilot study. J Chemother. 2011;23(6):358–61.PubMed
7.
Zurück zum Zitat Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan study group. N Engl J Med. 2000;343:905–14.PubMedCrossRef Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan study group. N Engl J Med. 2000;343:905–14.PubMedCrossRef
8.
Zurück zum Zitat Sunakawa Y, Ichikawa W, Fujita K, et al. UGT1A1*1/*28 and *1/*6 genotypes have no effects on the efficacy and toxicity of FOLFIRI in Japanese patients with advanced colorectal cancer. Cancer Chemother Pharmacol. 2011;68:279–84.PubMedCrossRef Sunakawa Y, Ichikawa W, Fujita K, et al. UGT1A1*1/*28 and *1/*6 genotypes have no effects on the efficacy and toxicity of FOLFIRI in Japanese patients with advanced colorectal cancer. Cancer Chemother Pharmacol. 2011;68:279–84.PubMedCrossRef
9.
Zurück zum Zitat Shulman K, Cohen I, Barnett-Griness O, et al. Clinical implications of UGT1A1*28 genotype testing in colorectal cancer patients. Cancer. 2011;117:3156–62.PubMedCrossRef Shulman K, Cohen I, Barnett-Griness O, et al. Clinical implications of UGT1A1*28 genotype testing in colorectal cancer patients. Cancer. 2011;117:3156–62.PubMedCrossRef
10.
Zurück zum Zitat Martinez-Balibrea E, Abad A, Martínez-Cardús A, et al. UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy. Br J Cancer. 2010;103:581–9.PubMedCrossRef Martinez-Balibrea E, Abad A, Martínez-Cardús A, et al. UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy. Br J Cancer. 2010;103:581–9.PubMedCrossRef
11.
Zurück zum Zitat Takano M, Kato M, Yoshikawa T, et al. Clinical significance of UDP-glucuronosyltransferase 1A1*6 for toxicities of combination chemotherapy with irinotecan and cisplatin in gynecologic cancers: a prospective multi-institutional study. Oncology. 2009;76:315–21.PubMedCrossRef Takano M, Kato M, Yoshikawa T, et al. Clinical significance of UDP-glucuronosyltransferase 1A1*6 for toxicities of combination chemotherapy with irinotecan and cisplatin in gynecologic cancers: a prospective multi-institutional study. Oncology. 2009;76:315–21.PubMedCrossRef
12.
Zurück zum Zitat Park SR, Kong SY, Rhee J, et al. Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results. Ann Oncol. 2011;22:890–6.PubMedCrossRef Park SR, Kong SY, Rhee J, et al. Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results. Ann Oncol. 2011;22:890–6.PubMedCrossRef
13.
Zurück zum Zitat Gao J, Zhou J, Li Y, et al. UGT1A1*6/*28 polymorphisms could predict irinotecan-induced severe neutropenia not diarrhea in Chinese colorectal cancer patients. Med Oncol. 2013;30(3):604–9.PubMedCrossRef Gao J, Zhou J, Li Y, et al. UGT1A1*6/*28 polymorphisms could predict irinotecan-induced severe neutropenia not diarrhea in Chinese colorectal cancer patients. Med Oncol. 2013;30(3):604–9.PubMedCrossRef
14.
Zurück zum Zitat Liu CY, Chen PM, Chiou TJ, et al. UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma. Cancer. 2008;112:1932–40.PubMedCrossRef Liu CY, Chen PM, Chiou TJ, et al. UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma. Cancer. 2008;112:1932–40.PubMedCrossRef
15.
Zurück zum Zitat Ferraldeschi R, Minchell LJ, Roberts SA, et al. UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. Pharmacogenomics. 2009;10:733–9.PubMedCrossRef Ferraldeschi R, Minchell LJ, Roberts SA, et al. UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. Pharmacogenomics. 2009;10:733–9.PubMedCrossRef
16.
Zurück zum Zitat Schulz C, Heinemann V, Schalhorn A, et al. UGT1A1 gene polymorphism: impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer. World J Gastroenterol. 2009;15:5058–66.PubMedCrossRef Schulz C, Heinemann V, Schalhorn A, et al. UGT1A1 gene polymorphism: impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer. World J Gastroenterol. 2009;15:5058–66.PubMedCrossRef
17.
Zurück zum Zitat Glimelius B, Garmo H, Berglund A, et al. Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer. Pharmacogenomics J. 2011;11:61–71.PubMedCrossRef Glimelius B, Garmo H, Berglund A, et al. Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer. Pharmacogenomics J. 2011;11:61–71.PubMedCrossRef
18.
Zurück zum Zitat Jada SR, Lim R, Wong CI, et al. Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C > A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci. 2007;98:1461–7.PubMedCrossRef Jada SR, Lim R, Wong CI, et al. Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C > A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci. 2007;98:1461–7.PubMedCrossRef
19.
Zurück zum Zitat Satoh T, Ura T, Yamada Y, et al. Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms. Cancer Sci. 2011;102:1868–73.PubMedCrossRef Satoh T, Ura T, Yamada Y, et al. Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms. Cancer Sci. 2011;102:1868–73.PubMedCrossRef
20.
Zurück zum Zitat Marcuello E, Páez D, Paré L, et al. A genotype-directed phase I-IV dose-finding study of irinotecan in combination with fluorouracil/leucovorin as first-line treatment in advanced colorectal cancer. Br J Cancer. 2011;105:53–7.PubMedCrossRef Marcuello E, Páez D, Paré L, et al. A genotype-directed phase I-IV dose-finding study of irinotecan in combination with fluorouracil/leucovorin as first-line treatment in advanced colorectal cancer. Br J Cancer. 2011;105:53–7.PubMedCrossRef
21.
Zurück zum Zitat Cortejoso L, García MI, García-Alfonso P, et al. Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer. Cancer Chemother Pharmacol. 2013; doi:10.1007/s00280-013-2145-6. Cortejoso L, García MI, García-Alfonso P, et al. Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer. Cancer Chemother Pharmacol. 2013; doi:10.​1007/​s00280-013-2145-6.
Metadaten
Titel
Associations between UGT1A1*6/*28 polymorphisms and irinotecan-induced severe toxicity in Chinese gastric or esophageal cancer patients
verfasst von
Jing Gao
Jun Zhou
Yanyan Li
Zhi Peng
Yilin Li
Xicheng Wang
Lin Shen
Publikationsdatum
01.09.2013
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 3/2013
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0630-8

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