Successful treatment of persistent bronchorrhea by gefitinib in a case with Recurrent Bronchioloalveolar Carcinoma: a case report
© Takao et al; licensee BioMed Central Ltd. 2003
Received: 23 April 2003
Accepted: 01 July 2003
Published: 01 July 2003
Bronchorrhea is one of late complaints in patients with bronchioloalveolar carcinoma (BAC) and hampers their quality of life. Although an effective treatment for bronchorrhea in these patients has not been established, recently we have treated effectively one case of persistent bronchorrhea associated with clinical recurrent BAC with gefitinib (ZD1839, 'Iressa™'; AstraZeneca Japan; Osaka, Japan).
A 63-year-old Japanese female had undergone left pneumonectomy with radical lymph node dissection (ND2a) for diffuse type bronchioloalveolar carcinoma originated in left lower lobe. Multiple pulmonary metastases in right lung were found one year after operation. Pulmonary metastatic lesion has grown and she complained of progressive symptoms of massive watery sputum and dyspnea, four years after operation. Although her symptom was getting worse in spite of routine treatment, it completely disappeared within 2 weeks of starting oral gefitinib. Thereafter, she has been symptom-free and shows good partial response on repeat scan after 9 months of oral gefitinib.
The dramatic remission of persistent bronchorrhea by gefitinib in the presented case suggests that gefitinib might be a promising option for bronchioloalveolar carcinoma, particularly in cases with severe bronchorrhea. Although it is not possible to comment on whether the improvement came from tumor cell death itself or suppressive effect of mucin synthesis by the epidermal growth factor receptor-tyrosine kinase inhibitory action.
Gefitinib is an oral active, selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) , which was first approved in Japan for patients with non-small cell lung cancer on July 5, 2002. It is very interesting that gefitinib is more effective in female patients with adenocarcinoma than the others . We describe here case of a female successfully treated with gefitinib for her persistent bronchorrhea due to recurrent multiple pulmonary bronchioloalveolar carcinoma (BAC) following left pneumonectomy.
She is taking daily 250 mg gefitinib for 9 months and had been very well without any signs of tumor progression or adverse side effects.
Gefitinib is an orally active, selective EGFR-TKI that blocks signal transduction pathways implicated in proliferation and survival of cancer cells . Although the mechanism has been uncertain, the response rate was significantly higher in adenocarcinoma and female patients than in squamous carcinoma and male ones in clinical experiences with gefitinib for lung cancer including two randomized double-blind phase II studies (IDEAL 1 and 2) [2, 3]. As clinical experience in Japan thereafter shows same tendency that gefitinib is more effective in female patients with adenocarcinoma, we tried gefitinib in this case. The response was somewhat more rapid and powerful than we expected. It is also true that the clinical effect is evident within the first few weeks if sensitive to gefitinib .
Although we have no evidence of a recurrent BAC in this case, we believe, such a quick response with gefitinib therapy strongly suggest her symptom with pulmonary consolidation had come from recurrence rather than infectious disease or drug-induced pneumonitis. It is meaningful if histological type BAC was associated with a higher response to gefitinib, because BAC that is usually resistant against chemotherapy and radiation brings respiratory failure and infection due to mucus hyper secretion in the end. Of particular, an effective treatment for refractory bronchorrhea in these patients has not been established, although a few successful case reports are available .
Our observation, although just single case report, may raises the possibility that the response in bronchorrhea due to BAC might be related to that association of the selective EGFR-TKI inhibition by gefitinib, because EGFR expression and activation is reported to cause goblet-cell metaplasia from Clara cells and mucus hyper secretion in the airway . So that, while it is still unknown whether the improvement of CT findings in our case comes from tumor cell death itself or suppressive effect of mucin synthesis by the EGFR-TKI action, the dramatic effect in our case brought us the hypothesis that gefitinib might be the promising option for BAC, of particular cases with severe bronchorrhea.
Although one might be also anticipate a high response to gefitinib in BAC subtype because BAC has even higher coexpression of both EGFR and HER2 than adenocarcinoma , clinical markers of gefitinib sensitivity should be investigated along with molecular predictive marker. Finally, in this sense, further investigations should be warranted for gefitinib, a unique and potent new type oral anti-cancer agent.
Conflict of interest
Written consent was obtained from the patient for publication of study.
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