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Open Access 01-06-2016 | Original Article

The combination of HLA-B15:01 and DRB115:01 is associated with gemcitabine plus erlotinib-induced interstitial lung disease in patients with advanced pancreatic cancer

Authors: Meiko Nishimura, Masanori Toyoda, Kei Takenaka, Yoshinori Imamura, Naoko Chayahara, Naomi Kiyota, Toru Mukohara, Takeshi Kotake, Akihito Tsuji, Kosuke Saito, Yoshiro Saito, Hironobu Minami

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2016

Abstract

Purpose

In a phase III study of gemcitabine plus erlotinib for advanced pancreatic cancer conducted in Canada, the incidence of interstitial lung disease (ILD) was 3.5 %. However, the incidence of ILD was reported as high as 8.5 % in a Japanese phase II study. These results suggest the influence of ethnic factors in the association of the use of gemcitabine plus erlotinib with the incidence of ILD. Here, we conducted a prospective study to analyze the relationship between human leukocyte antigen (HLA) alleles and ILD in Japanese patients with advanced pancreatic cancer receiving gemcitabine plus erlotinib.

Methods

Patients were treated with gemcitabine (1000 mg/m²; administered by intravenous infusion on days 1, 8, and 15 every 4 weeks) and erlotinib (given orally at 100 mg/day). We compared the frequencies of HLA alleles in patients who did and did not develop ILD.

Results

A total of 57 patients were treated, and 4 patients (7.0 %) developed ILD. The combination of HLA-B*15:01 and DRB1*15:01 was observed in 2 of 4 patients (50 %) with ILD and in only 1 of 53 patients without ILD (2 %) resulting in odds ratio of 52.0 (95 % CI 3.2–842.5; p = 0.011).

Conclusion

These results suggest that the combination of HLA-B*15:01 and DRB1*15:01 is associated with ILD in Japanese patients with advanced pancreatic cancer receiving gemcitabine plus erlotinib.

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Title: The combination of HLA-B*15:01 and DRB1*15:01 is associated with gemcitabine plus erlotinib-induced interstitial lung disease in patients with advanced pancreatic cancer
Authors: Meiko Nishimura
Masanori Toyoda
Kei Takenaka
Yoshinori Imamura
Naoko Chayahara
Naomi Kiyota
Toru Mukohara
Takeshi Kotake
Akihito Tsuji
Kosuke Saito
Yoshiro Saito
Hironobu Minami
Publication date: 01-06-2016
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3026-6

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