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. 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.

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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

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