ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity
| Autor: | Hiroyuki Mano, Hideki Kimura, Kengo Takeuchi, Sana Yokoi, Takahiro Nakajima, Manabu Soda, Akira Nakagawara, Meiji Itakura, Hajime Kageyama, Yukiko Matsui, Toshihiko Iizasa, Miki Ohira, Masato Shingyoji, Makiko Itami, Mitsuru Yoshino, Dai Ikebe |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Oncology Cancer Research medicine.medical_specialty Pathology Lung Neoplasms Oncogene Proteins Fusion medicine.drug_class medicine.medical_treatment Kinesins Adenocarcinoma of Lung Cell Cycle Proteins Adenocarcinoma Carcinoma Non-Small-Cell Lung hemic and lymphatic diseases Internal medicine medicine Carcinoma Humans Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Neoplasm Metastasis Kinase activity Lung cancer Protein Kinase Inhibitors Aged Neoplasm Staging Aged 80 and over Chemotherapy Crizotinib business.industry Serine Endopeptidases Receptor Protein-Tyrosine Kinases Middle Aged Protein-Tyrosine Kinases medicine.disease Immunohistochemistry ALK inhibitor Female Gene Fusion business Microtubule-Associated Proteins medicine.drug |
| Zdroj: | Lung Cancer. 75:66-72 |
| ISSN: | 0169-5002 |
| DOI: | 10.1016/j.lungcan.2011.05.027 |
| Popis: | Background Anaplastic lymphoma kinase (ALK) fusion gene-positive lung cancer accounts for 4–5% of non-small cell lung carcinoma. A clinical trial of the specific inhibitor of ALK fusion-type tyrosine kinase is currently under way. Methods ALK fusion gene products were analyzed immunohistochemically with the materials obtained by surgery or by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The echinoderm microtubule-associated protein-like 4(EML4)-ALK or kinesin family member 5B (KIF5B)-ALK translocation was confirmed by the reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). After eligibility criteria were met and informed consent was obtained, 3 patients were enrolled for the Pfizer Study of Crizotinib (PF02341066), Clinical Trial A8081001, conducted at Seoul National University. Results Out of 404 cases, there were 14 of EML4-ALK non-small cell carcinoma (NSCLC) and one KIF5B-ALK NSCLC case (8 men, 7 women; mean age, 61.9 years, range 48–82). Except for 2 light smokers, all patients were non-smokers. All cases were of adenocarcinoma with papillary or acinar subtypes. Three were of stage IA, 5 of stage IIIA, 1 of stage IIIB and 6 of stage IV. Ten patients underwent thoracotomy, 3 received chemotherapy and 2 only best supportive care (BSC). One BSC and 2 chemotherapy cases were enrolled for the clinical trial. Patients with advanced stages who received chemotherapy or best supportive care were younger (54.0 ± 6.3) than those who were surgically treated (65.8 ± 10.1) (p The powerful effect of ALK inhibitor on EML4-ALK NSCLC was observed. Soon after its administration, almost all the multiple bone and lymph node metastases quickly disappeared. Nausea, diarrhea and the persistence of a light image were the main side effects, but they diminished within a few months. Conclusion ALK-fusion gene was found in 3.7% (15/404) NSCLC cases and advanced disease with this fusion gene was correlated with younger generation. The ALK inhibitor presented in this study is effective in EML4-ALK NSCLC cases. A further study will be necessary to evaluate the clinical effectiveness of this drug. |
| Databáze: | OpenAIRE |
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