Bronchioloalveolar carcinoma (BAC) and adenocarcinoma mixed subtype with bronchioloalveolar features (ADC-WBF) represent a unique anatomo-clinical entity accounting for some 20% of non-small cell lung cancers (NSCLC). These tumors seem less sensitive to chemotherapy than other NSCLC. We report two cases of advanced ADC-WBF treated with second-line and fourth-line pemetrexed. Major and durable radiological response associated with clinical and functional improvement was achieved in both patients, without important drug toxicity. After treatment arrest, the two patients experienced progressive disease but responded to retreatment with pemetrexed. Recent data suggest that paclitaxel-based chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors could be an acceptable therapeutic strategy in unresectable CBA and ADC-WBF. The cases reported here and preclinical findings suggest a therapeutic efficacy of pemetrexed in these tumors. Prospective studies are required to evaluate this hypothesis.
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