Targeted Therapy with an EGFR Tyrosine Kinase Inhibitor in Bronchioloalveolar Carcinoma of the Lung: A Literature Review and a Case Study of Clinically Prompt and Intensive Response to Erlotinib.
Authors:
M. Svoboda 1,2; P. Fabian 3; O. Slabý 1,2; M. Staňková 4; R. Lakomý 1,2; R. Němeček 1; R. Vyzula 1,2
Authors‘ workplace:
Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno
1; Lékařská fakulta Masarykovy Univerzity, Brno
2; Oddělení patologie, Masarykův onkologický ústav, Brno
3; Institute of Applied Biotechnologies, a. s., Praha
4
Published in:
Klin Onkol 2010; 23(4): 224-230
Category:
Reviews
Overview
Introduction:
Bronchioloalveolar carcinoma (BAC) is an adenocarcinoma belonging to non-small cell lung carcinomas (NSCLC) that, in addition to its morphology and endobronchial spread, presents with certain specific clinical characteristics: greater incidence in women, non-smokers and younger patients, presence of malignant bronchorrhea and lower susceptibility to conventional cytostatic therapies in comparison to other subtypes of NSCLC. On the other hand, nonmucinous type of BAC may show better therapeutic response to targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) erlotinib or gefitinib, as it is 5 times more frequently a carrier of EGFR gene mutations compared to conventional lung adenocarcinomas.
Case description:
We present a case of a 41 years old man, non-smoker for the last 5 years, who was diagnosed with a pneumonic form of nonmucinous bronchioloalveolar carcinoma. Metastases to regional and distant lymph nodes and massive involvement of skeleton with infiltrations in the bone marrow were present at the diagnosis. During the first line palliative chemotherapy with combination regimen of carboplatin and paclitaxel, the disease progressed significantly and the patient’s condition deteriorated (performance status (PS) 3, severe dyspnoea at rest, malignant bronchorrhea). Subsequently, administration of erlotinib was initiated based on a series of case studies describing good response of BAC to treatment with EGFR TKI. An evident improvement of the patient’s condition was observed as early as 4 days of administration, together with regression of peripheral lymphadenopathy. Nearly complete disappearance of pulmonary infiltrates was observed after 30 days of therapy, with the patient becoming asymptomatic, PS 0. Molecular genetics confirmed the tumour phenotype to be highly responsive to EGFR TKI therapy. The tumour contained EGFR mutation in exon 19 (in-frame L747-753insS deletion) and wild-type K-ras. Disease relapse in the liver occurred 6 months later confirming disease progression. Further treatment remained ineffective despite brief stabilisations of liver enzyme progression following repeated administration of pemetrexed and gefitinib. The patient died 12 months after the diagnosis.
Conclusions:
Our case confirms the importance of targeted therapy when treating tumours of an appropriate phenotype. Such treatment may have prompt and intensive effect that may reverse the course of the disease even in patients with poor overall health status.
Key words:
lung cancer – bronchioloalveolar carcinoma – EGFR gene – K-ras gene – erlotinib – gefitinib – targeted therapy – prediction
Sources
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Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2010 Issue 4
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