非小細胞肺癌的標靶治療

(1)

112 201

( targeted therapy ) ( oncogenesis )

( epidermal growth factor receptor tyrosine kinase inhibitor EGFR-TKI )

E G F R ( epidermal growth

factor receptor monoclonal antibody EGFR-moAb )

( vascula r endot helia l growth factor monoclonal antibody VEGF-moAb )

( Non-small cell lung cancer ) ( Targeted therapy )

( Epidermal growth factor receptor ) ( Tyrosine kinase inhibitor )

( Vascular endothelial growth factor ) ( Monoclonal antibody )

( non-small cell lung cancer ) 8 5 %

( cisplatin carboplat in )

(2)

( gemcitabine ) ( paclitax-

el ) ( docetaxel ) ( vinorel-

bine ) ( doublets )

1

( Epidermal Growth Factor Receptor Inhibition, EGFRI )

E G F R 2 0 M e n d e l s o h n

(overexpression ) E G F R

²

E G F R

( ligand-binding domain )

( tyrosine kinase ) E G F R

E G F R 4 3 %

8 9 %

³

E G F R

1. ( Tyrosine kinase inhibitors, TKIs ) :

( EGFR-TK ) ( reversibly )

gefitinib ( Iressa ) erlotinib (

Tarceva )

( 1 ) Gefitinib ( Iressa, )

g e f i t i n i b

4 , 5

( Iressa Dose Evaluation in Advanced Lung Cancer 1, 2 IDEAL 1, IDEAL 2 )

2 5 0 5 0 0 g e f i t i n i b IDEAL 1 2 1 0

g e f i t i n i b 17% ( 250mg ) 18% ( 500mg )

2 5 0

2 7 . 5 % 1 0 . 4 %

I DEAL 1 2 0 0 2 7

( interst itial pneumonit is )

6 , 7

4 . 6 %

1 % ( 1.5% )

X

8

IDEAL 2 2 2 1

12% ( 250mg ) 9% ( 500mg )

( accelerat- ed approval regulations )

2 0 0 3 5

( AstraZeneca )

( Ire ssa S ur vi val

Evaluation i n Lung Cancer, ISEL )

⁹

(3)

I N TACT 1, INTACT 2 ( Ire ssa NS CLC Tri al Assessing Combi nat ion Treatment 1and 2 )

^{1 0 , 11}

( chemo-naive )

2 0 0 4 1 2 I S E L

( never smoker )

1 2

( Marketing Authorization Application ) 2 0 0 5 6

1 3

( Alert for Healthcare Professionals )

2 0 0 2 2 0 0 4

( ade- nocarcinoma of lung )

2 2 . 7 %

^{1 4}

2 . 8 % 2 0 0 6

( 2 ) Erlotinib ( Tarceva )

( maximum-tol- erated dose ) 150 mg/day

1 5

BR. 21

150 mg/day

( 9% ) ( 6.7 vs 4.7 months, p<0.001 )

2 0 0 4 1 2

T R I B U T E

^{1 6}

TA L E N T

^{1 7}

2 0 0 6 2 0 0 7

3 ( ISEL vs BR.21 )

150 mg/day 250 mg/day

I S E L

^{9 , 1 5}

I S E L 3 9 %

( progressive di sease ) B R . 2 1 2 8 %

9 , 1 5

( 3 ) ( EGFR mutation )

2 0 0 4

( exon )18 2 1 E G F R - T K I

1 8 , 1 9

( somatic c ell s )

E R F R - T K I

^{2 0}

( 1 ). 1 9 ( deletion )

E G F R 4 6 % ( 2 ).

2 1 ( missense mutation )

4 1 % ( 3 ).

2 0 ( dupli cation/inse rt ion )

5 % E G F R

(4)

E G F R E G F R E G F R

- T K I

^{2 1}

E G F R

E G F R - T K I

2 . (EGFR monoclon-

al antibody ) E G F R

( transforming growth factor- ,

T G F - ) ( epidermal growth

f a c t o r, EGF )

Ce t ux i ma b (

E r bi t u x ) ( hu ma n-

murine chimeric ) T G F -

E G F E G F R C e t u x i m a b

( additive and synergistic )

^{2 2}

C e t u x i m a b

4 0 0 ( 400 mg/m

²

) 2 5 0 ( 250 mg/m

²

)

( 21% ) ( 13.5% ) ( 13.5% )

( 11.5% ) ( 11.5% )

^{2 3}

C e t u x i m a b

4 . 5 % ( disease-cont rol rate ) ( ov e r a l l su r vi va l )

E r l o t i n i b

^{2 4}

C e t u x i m a b

2 5

E G F R

c e t u x i m a b

2 0 0 7

( VEGF monoclonal antibody )

2

^{2 6}

2 7

( VEGF )

Bevacizumab ( Avastin ) V E G F

c a r b o p l a t i n p a c l i t a x e l bevacizumab 7.5 m g / k g 15 mg/kg c a r b o p l a t i n p a c l i- t a x e l

bevacizumab 15 mg/kg ( time to progression )

2 8

B e v a c i z u m a b

b e v a -

c i z u m a b 6 6 6

9 . 1 % 4

b e v a c i z u m a b

( squamous cell carcinoma of lung )

( cavi t ati on )

b e v a c i z u m- a b c a r b o p l a t i n p a c l i t a x e l

2 9

b e v a c i z u m a b

4 . 4 %

( significant bleeding ) 1 . 9 %

b e v a c i z u m a b

(5)

E G F R

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Targeted Therapy in Non-small Cell Lung Cancer

Ying-Ming Shih, and Yuh-Min Chen

¹

Chemotherapy or radiotherapy is the mainstay of management for advanced non-small cell lung cancer.

However, the treatment induces toxicity often affecting the patient's quality of life. The new developing targeted

therapies are designed to interfere with specific molecules involved in oncogenesis. Epidermal growth factor re-

ceptor tyrosine kinase inhibitor is the first drug of targeted therapy approved for patients with advanced or metastat-

ic non-small cell lung cancer after failure of at least one prior chemotherapy. The common side effects include

skin rash and diarrhea. Interstitial pneumonitis has been reported and might lead to mortality. The response rates

are higher in Asian populations, women, adenocarcinoma, never smokers and EGFR mutations. Epidermal growth

factor receptor monoclonal antibody has been shown survival benefit in advanced NSCLC during phase II trials

but lacks of large randomized phase III studies. Vascular endothelial growth factor monoclonal antibody com-

bined with carboplatin and paclitaxel in the treatment of naive advanced NSCLC has significant survival benefit

and response rate but increases the risk of pulmonary hemorrhage, especially in squamous cell carcinoma of

lung. ( J Intern Med Taiwan 2008; 19: 8- 13 )