Bronchioloalveolar carcinoma: A model for investigating the biology of epidermal growth factor receptor inhibition

• Published in: Clinical cancer research Vol. 10; no. 12; pp. 4205s - 4209s
• Main Authors: GANDARA, David R, WEST, Howard, CHANSKY, Kari, DAVIES, Angela M, LAU, Derick H. M, CROWLEY, John, GUMERLOCK, Paul H, HIRSCH, Fred R, FRANKLIN, Wilbur A
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.06.2004
• Subjects: Adenocarcinoma, Bronchiolo-Alveolar - physiopathology; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - analysis; Clinical Trials as Topic; Humans; Lung Neoplasms - physiopathology; Medical sciences; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; Pharmacology. Drug treatments; Prognosis; Quinazolines - administration & dosage; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - drug effects; Receptor, Epidermal Growth Factor - physiology; Signal Transduction; Tumors; Biology; Inhibitor; Models; Epidermal growth factor receptor; Bronchioloalveolar carcinoma
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-040012

Bronchioloalveolar carcinoma (BAC) is a previously uncommon subset of non-small cell lung cancer (NSCLC) with unique epidemiology, pathology, clinical features, radiographic presentation, and natural history compared with other NSCLC subtypes. Recent data suggest that the incidence of BAC is increasing, notably in younger nonsmoking women. Despite reports of prolonged survival after repeated surgical resection of multifocal lesions and slow growth kinetics, advanced bilateral or recurrent diffuse BAC remains incurable, with the vast majority of patients dying of respiratory failure or intercurrent pneumonia within 5 years. Limited data suggest that chemotherapy may yield poor results in BAC. However, anecdotal reports of prolonged complete response to tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR), a member of the human epidermal growth factor receptor (erbB) family, have raised considerable interest in studying this NSCLC subset. Here we present clinical data and preliminary results of correlative science studies analyzing human epidermal growth factor receptor pathways from the following two prospective Southwest Oncology Group clinical trials performed in advanced stage BAC: S9714 testing a 96-h continuous infusion of paclitaxel (Taxol) and S0126 evaluating the small molecule EGFR inhibitor gefitinib (ZD1839 or Iressa). These studies provide a biological rationale for investigating BAC as a model of predictive markers of EGFR inhibition.