non-small-cell lung cancer NSCLC CT 85% CT MRI NSCLC cm 2 cm EGFR TKI T2 EGFR-TKI EGFR Ⅲ ~ Ⅳ 3

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1 EGFR-TKI EGFR-TKI EGFR-TKI Ⅲ ~ Ⅳ 7 1 SD NSCLC R A Successful treatment of one patient with advanced non-small cell lung cancer with icotinib hydrochloride in replacement of gefitinib ZHANG Li 1 GUAN Qiu-hong 2 ZHAO Yan-wei 1 XIA Ying 1 XIAO Yi 1 1 Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine Beijing China 2 Chinese Academy of Medical Science Peking Union Medical College Hospital Beijing China Abstract Common adverse reactions of epidermal growth factor receptor tyrosine kinase inhibitor EGFR- TKI due to drug toxicity are rash and diarrhea. Positive curative effect has been observed after gefitinib Iressa ZD1839 and erlotinib Tarceva Ro were introduced into China in 2005 and 2007 respectively. However some patients who were likely to benefit from the therapy might not accept EGFR-TKIs because of severe adverse event AE during the treatment. Conmana icotinib hydrochloride BPI-2009H is a newly developed and highly specific EGFR-TKI that is designed in China with independent intellectual property right. In this case the patient experienced III ~ IV-level diarrhea after taking gefitinib and antidiarrheal drugs were ineffective. The intolerable AE led to drug withdrawal. Treatment was then transformed into icotinib therapy and had been on for 7 months without apparent AE observed. After the first cycle of icotinib 30 days objective responses were evaluated to be SD physical conditions and the quality of life were improved. This suggests that icotinib is effective and well-tolerated in advanced NSCLC patients and superior to gefitinib and erlotinib in terms of curative effectiveness and safety among Chinese patients. Key words epidermal growth factor receptor tyrosine kinase inhibitor non-small cell lung cancer icotinib hydrochloride severe diarrhea 张力, 女, 硕士生导师, 主任医师, 教授, 主要从事呼吸系统肿瘤的研究联系电话 : ( 010) , zhanglipumch@ yahoo. com. cn 关秋红, 女, 博士, 副主任医师, 主要从事中西医结合防治肺癌联系电话 : ( 010) , guanqh1969@ yahoo. com. cn 张力和关秋红为并列第一作者 1676

non-small-cell lung cancer NSCLC 2011 4 15 CT 85% 1 2011 4 16 CT MRI + 2 - NSCLC 3 1. 5 cm 2 cm EGFR TKI T2 EGFR-TKI EGFR 2011 4 28 3 2011 6 9 Ⅲ ~ Ⅳ 38 121 mmol L - 1 2011 6 13 CT 1 2 cm 3.

2 non-small-cell lung cancer NSCLC CT 85% CT MRI NSCLC cm 2 cm EGFR TKI T2 EGFR-TKI EGFR Ⅲ ~ Ⅳ mmol L CT 1 2 cm 3. 1 cm 1a ~ d MRI 1. 9 cm 0. 9 cm cm 2 a ~ c CT Exon21 L858R 2573T > G mmol L h 198 mmol L - 1 scorpions amplification refractory mutation system SARMS EGFR μg 250 mmol L h UFC ACTH 1677

3 17. 8 pg ml ng ml - 1 < ml d - 1 3% 500 ml 20 mg SIADH mmol L mg qd 600 mg po qd mg g tid mg L mg po qd mg 6 h 1 2 mg 72 h g L L mg tid g tid 2 mg tid 3 g tid h U-K mol L -1 U-Na 388 mol L -1 U-Cl 234 mol L mosm kg -1 H 2 O MRI T mg po bid WBC L L mg iv mg po tid CT 28 CT 3a ~ d MRI PD a ~ c SD CT SD CT 1678

4 PD NCCN % EGFR-TKI NSCLC % EGFR-TKI 85 EGFR 3 IC EGFR-TKI nmol L - 1 IC ~ 90 nmol L mg kg % 56% 38% Ⅲ ~ Ⅳ ADH SIADH EGFR Exon21 L858R 2573 T > G SIADH mmol L < mg qd mg bid 1 SIADH 125 mg tid 7 1 CT SD CT Ⅳ NSCLC 8 ~ 10 PFS 7 8 PFS IV PFS mg qd mg bid mg tid PFS 3 ~ 4 SAE 10 EGFR-TKI 7 11 I ~ III CT 3 NSCLC III 60. 5% 1679

5 70. 4% 18. 5% 27. 6% 3 GAZDAR AF. Personalized medicine and inhibition of egfrsignal % 49. 2% 8. 0% 12. 6% CTC ing in lung cancer J ZHOU Q SHEN J SHENTU J et al. AphaseⅠ /Ⅱa study of icotinib by drochloride anoveloral EGFR-TKI to evaluateits safety tolerance and preliminary efficacy in advanced NSCLC patients in China J. J Clin Oncol s ab- 32% I II 96% str III J mg qd 150 mg qd 250 mg qd tid LANGER C J METHA MP. Current management of brain metas- NSCLC tases with a focus on system options J EGFR 11 NSCLC / J ROSELL R MORAN T QUERALT C et al. Screening for epidermal growth factor receptor mutations in lung cancer J. N Engl J Med N Engl J Med NSCLC D NJAY P SARAH H PANOS P et al. Responses to non-small cell lung cancer brain metastases with erlotinib J. Lung Cancer J.. J J Clin Oncol J SUN Y. ASCO 2011 and WCLC 2011 C HERBST RS HEYMACH JV LIPPMAN SM. Lungcancer J. N Engl J Med / 檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼檼 FLEISCHMANN R CUTOLO M GENOVESE MC et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib CP or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs J. Arthritis Rheum FLEISCHMANN R KREMER J CUSH J et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis J. N Engl J Med VAN VOLLENHOVEN RF FLEISCHMANN R COHEN S et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis J. N Engl J Med BURMESTER GR BLANCO R CHARLES-SCHOEMAN C et al. Tofacitinib CP in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors a randomised phase 3 trial J. Lancet WOLLENHAUPT J SILVERFIELD JC LEE EB et al. Tofacitinib CP an oral janus kinase inhibitor the treatment of rheumatoid arthritis open-label long-term extension studies up to 36 months J. Arthritis Rheum Suppl 10 S152 - S153. /

臨床藥物治療學 Therapeutics of Clinical Drugs ( 5% 10%) 3 EGFRIs ( ) 4 (10-17%) TKI (5-9%) ( clindamycin 1%) doxycycline 100 mg minocycline 100 mg isot

臨床藥物治療學 Therapeutics of Clinical Drugs ( 5% 10%) 3 EGFRIs ( ) 4 (10-17%) TKI (5-9%) ( clindamycin 1%) doxycycline 100 mg minocycline 100 mg isot Therapeutics of Clinical Drugs 臨床藥物治療學表皮生長因子抑制劑皮膚併發症中山醫學大學附設醫院藥劑科藥師林政仁吳雀維中山醫學大學附設醫院醫師劉親穎摘要 (epidermal growth factor receptor inhibitors EGFRIs)