104

73 2 : 104-110, 2015

Interstitial lung disease induced by molecular targeted drugs

Akinobu YOSHIMURA

Department of Clinical Oncology, Tokyo Medical University Hospital

1

27 1 17 27 3 13: Molecular targeted drugs interstitial lung disease epidemiology

CT high resolution CT: 160-0023 6-7-1

TEL : 03-3342-6111 2161 FAX : 03-3342-6211

EGFREGFR-TKI

Bevacizumab SunitinibEGFR-TKI

EGFR-TKI

1.

PMDA1 1

2009

25%

: 1052015 4

50%1

2-17

AfatinibCrizotinib Alectinib Imatinib

Gemcitabine 1.7% Pemetrexed3.6%

1% 1Sorafenib Sunitinib Bevacizumab

5% 1.2-

22.9%

EGFR-TKI Ge -tinib Erlotinib

39% 75/193 37% 153/429EGFR Cetuximab Panitumumab1.2% 1.3%

42% 10/24 63% 20/39mTOR

Everolimus Temsirolimus22.9% 7.8%

3.3% 8/244 7.7% 6/78

Ge tinib PS2 Erlotinib

COPDPS2 2 3

Ge tinib

Ge tinib3.2

Ge tinib PS

18 Ge tinib

EGFR-TKI5.8% 0.3% 20

19

Bleomycin0.01%

2

1 1

73 2106

0.66% 60 19

EGFR-TKI

20 EGFR-TKI

DNADNA

MUC4EGFR-TKI

20

2.

2 21

diffuse alveolar damage ; DADorganizing pneumonia ; OPnonspeci c interstitial pneumonia ; NSIP

eosinophlic pneumonia ; EP

hypersensitivity pneumonia ; HP

3

1 2-17

Targets Drugs Incidence rate Mortality rate

Small-molecule targeted drugsEGFR Ge tinib* 5.8% 193/3,322 2.3% 75/3,322

Erlotinib* 4.3% 429/9,909 1.5% 153/9,909Afatinib** 3.1% 4/128

ALK Crizotinib** 1.8% 22/1,225 0.2% 3/1,225Alectinib** 1.7% 1/58 0.0% 0/58

BCR-ABL, KIT, PDGFR Imatinib*** < 5%Dasatinib* 2.9% 24/838Nilotinib* 1.3% 11/848 0.4% 3/848

VEGFR, PDGFR, FLT3 + Sorafenib* 0.4% 12/3,054 0.2% 6/3,054Sunitinib* 0.7% 15/2,141 0.1% 3/2,141

mTOR Everolimus* 22.9% 244/1,067 0.7% 8/1,067Temsirolimus* 7.8% 78/1,004 0.6% 6/1,004

Proteasome Bortezomib* 4.5% 45/1,010 0.5% 5/1,010

Monoclonal antibodiesEGFR Cetuximab* 1.2% 24/2,006 0.5% 10/2,006

Panitumumab* 1.3% 39/3,085 0.6% 20/3,085VEGF Bevacizumab* 0.4% 10/2,698 0.1% 2/2,698

According to post-marketing surveillance * , clinical study ** and pharmaceutical reference ***

2 1

11 2 3 4 5 6 7 8 9

123

2 12

3 123

4 1

: 1072015 4

orga-nizing DAD

22

3.

1 2

3 4 5

23

mTOR Everolimus Temsirolimus

ARDS

X 2 21

XCT KL-6 SP-A

4

2

73 2108

SP-D

-D-

KL-6 SP-A SP-D BNP

DLST

TBLB BAL

4.

TBLB BALCT CT high-resolution CT :

HRCTCT

21 24

25

26

3 21 24

3 21 24 27

21 22 24

5

3 CT

3 CT 21

: 1092015 4

21 24

5.

4 28

0.5 1.0 mg/kg/

5001,000 mg/ 30.5 1.0 mg/kg/ 28

B

29

mTOR Everolimus Temsirolimus

12 13

6

X

1 I

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