HLA - B*15:01与DRB1*15:01的组合与晚期胰腺癌患者接受吉西他滨联合厄洛替尼治疗后发生的间质性肺病相关。
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.
作者信息
Nishimura Meiko, Toyoda Masanori, Takenaka Kei, Imamura Yoshinori, Chayahara Naoko, Kiyota Naomi, Mukohara Toru, Kotake Takeshi, Tsuji Akihito, Saito Kosuke, Saito Yoshiro, Minami Hironobu
机构信息
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Cancer Center, Kobe University Hospital, Kobe, Japan.
出版信息
Cancer Chemother Pharmacol. 2016 Jun;77(6):1165-70. doi: 10.1007/s00280-016-3026-6. Epub 2016 Apr 21.
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-B15:01 and DRB115:01 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-B15:01 and DRB115:01 is associated with ILD in Japanese patients with advanced pancreatic cancer receiving gemcitabine plus erlotinib.
目的
在加拿大进行的一项吉西他滨联合厄洛替尼治疗晚期胰腺癌的III期研究中，间质性肺疾病（ILD）的发生率为3.5%。然而，在日本的一项II期研究中，ILD的发生率高达8.5%。这些结果提示种族因素对吉西他滨联合厄洛替尼使用与ILD发生率之间关联的影响。在此，我们进行了一项前瞻性研究，以分析接受吉西他滨联合厄洛替尼治疗的日本晚期胰腺癌患者中人类白细胞抗原（HLA）等位基因与ILD之间的关系。
方法
患者接受吉西他滨（1000mg/m²；每4周的第1、8和15天静脉输注）和厄洛替尼（每日口服100mg）治疗。我们比较了发生和未发生ILD的患者中HLA等位基因的频率。
结果
总共57例患者接受了治疗，4例（7.0%）发生了ILD。在4例发生ILD的患者中有2例（50%）观察到HLA - B15:01和DRB115:01的组合，而在53例未发生ILD的患者中仅1例（2%）出现该组合，优势比为52.0（95%CI 3.2 - 842.5；p = 0.011）。
结论
这些结果表明，在接受吉西他滨联合厄洛替尼治疗的日本晚期胰腺癌患者中，HLA - B15:01和DRB115:01的组合与ILD相关。
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