Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jun;77(6):1165-70.
doi: 10.1007/s00280-016-3026-6. Epub 2016 Apr 21.

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

Meiko Nishimura  1 , Masanori Toyoda  1 , Kei Takenaka  1 , Yoshinori Imamura  1 , Naoko Chayahara  1 , Naomi Kiyota  1 , Toru Mukohara  1   2 , Takeshi Kotake  3   4 , Akihito Tsuji  3   5 , Kosuke Saito  6 , Yoshiro Saito  6 , Hironobu Minami  7   8
Affiliations

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

Meiko Nishimura et al. Cancer Chemother Pharmacol. 2016 Jun.

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/m(2); 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.

Keywords: Erlotinib; Gemcitabine; Human leukocyte antigen; Interstitial lung disease; Pancreatic cancer.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
a Chest CT scans of a 65-year-old female non-smoker with lung and liver metastases at 8 weeks. b Chest CT scans of a 64-year-old female non-smoker with locally advanced cancer at 12 weeks. c Chest CT scans of a 76-year-old male ex-smoker with lung metastasis at 4 weeks. d Chest CT scans of a 70-year-old male ex-smoker with liver metastasis at 6 weeks
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W, National Cancer Institute of Canada Clinical Trials G Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15):1960–1966. doi: 10.1200/JCO.2006.07.9525. - DOI - PubMed
    1. Gemma A, Kudoh S, Ando M, Ohe Y, Nakagawa K, Johkoh T, Yamazaki N, Arakawa H, Inoue Y, Ebina M, Kusumoto M, Kuwano K, Sakai F, Taniguchi H, Fukuda Y, Seki A, Ishii T, Fukuoka M. Final safety and efficacy of erlotinib in the phase 4 POLARSTAR surveillance study of 10 708 Japanese patients with non-small-cell lung cancer. Cancer Sci. 2014;105(12):1584–1590. doi: 10.1111/cas.12550. - DOI - PMC - PubMed
    1. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L, National Cancer Institute of Canada Clinical Trials G Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123–132. doi: 10.1056/NEJMoa050753. - DOI - PubMed
    1. Tamiya A, Endo M, Shukuya T, Igawa S, Tsuya A, Nakamura Y, Murakami H, Takahashi T, Boku N, Yamamoto N. Features of gemcitabine-related severe pulmonary toxicity: patients with pancreatic or biliary tract cancer. Pancreas. 2009;38(7):838–840. doi: 10.1097/MPA.0b013e3181ad97cf. - DOI - PubMed
    1. Okusaka T, Furuse J, Funakoshi A, Ioka T, Yamao K, Ohkawa S, Boku N, Komatsu Y, Nakamori S, Iguchi H, Ito T, Nakagawa K, Nakachi K. Phase II study of erlotinib plus gemcitabine in Japanese patients with unresectable pancreatic cancer. Cancer Sci. 2011;102(2):425–431. doi: 10.1111/j.1349-7006.2010.01810.x. - DOI - PubMed

Publication types

MeSH terms