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.
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.



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.



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).



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.
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Meiko
M
Nishimura
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Masanori
M
Toyoda
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Kei
K
Takenaka
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yoshinori
Y
Imamura
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Naoko
N
Chayahara
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Naomi
N
Kiyota
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.|Cancer Center, Kobe University Hospital, Kobe, Japan.
Toru
T
Mukohara
Department of Medical Oncology, Kobe City Hospital Organization, Kobe City Medical Center General Hospital, Kobe, Japan.|Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan.
Takeshi
T
Kotake
Department of Medical Oncology, Kobe City Hospital Organization, Kobe City Medical Center General Hospital, Kobe, Japan.|Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Akihito
A
Tsuji
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Kosuke
K
Saito
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Yoshiro
Y
Saito
Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan. hminami@med.kobe-u.ac.jp.|Cancer Center, Kobe University Hospital, Kobe, Japan. hminami@med.kobe-u.ac.jp.
Hironobu
H
Minami
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D015796:HLA-B27 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011446:Prospective Studies; D055815:Young Adult; D000093542:Gemcitabine
C090660:HLA-B protein, human; D015796:HLA-B27 Antigen; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine
Erlotinib; Gemcitabine; Human leukocyte antigen; Interstitial lung disease; Pancreatic cancer