Bronchial colonisation in patients with lung cancer: a prospective study.

Bronchial colonisation is frequently reported in patients with lung cancer, and has a potential impact on therapeutic management and prognosis. We aimed to prospectively define the prevalence and nature of bronchial colonisation in patients at the time of diagnosing lung cancer. 210 consecutive patients with lung cancer underwent a flexible bronchoscopy for lung cancer. The type and frequency of bacterial, mycobacterial and fungal colonisation were analysed and correlated with the patients' and tumours' characteristics. Potential pathogens were found in 48.1% of samples: mainly the Gram-negative bacilli Escherichia coli (8.1%), Haemophilus influenzae (4.3%) and Enterobacter spp. (2.4%); Gram-positive cocci, Staphylococcus spp. (12.9%) and Streptococcus pneumoniae (3.3%); atypical mycobacteria (2.9%); Candida albicans (42.9%); and Aspergillus fumigatus (6.2%). Aged patients (p=0.02) with chronic obstructive pulmonary disease (p=0.008) were significantly more frequently colonised; however, tumour stage, atelectasis, bronchial stenosis and abnormalities of chest radiography were not associated with a higher rate of colonisation. Squamous cell carcinoma tended to be more frequently colonised than other histological subtypes. Airway colonisation was reported in almost half of patients presenting with lung cancer, mainly in fragile patients, and was significantly associated with worse survival (p=0.005). Analysing colonisation status of patients at the time of diagnosis may help improve the management of lung cancer.

In vivo and in vitro antitumor activity of oxaliplatin in combination with cetuximab in human colorectal tumor cell lines expressing different level of EGFR.

This study aimed to assess the effect of cetuximab (C225, Erbitux, a chimeric anti-epidermal growth factor receptor (EGFR) monoclonal antibody) in combination with oxaliplatin in vitro and in vivo on four colon cancer cell lines (HCT-8; HT-29, SW620, HCT-116) expressing different levels of EGFR. In vitro, cetuximab combined with oxaliplatin significantly decreased the IC50 values of oxaliplatin in HCT-8 (EGF-R moderate) and HT-29 (EGF-R weak) cell lines, while SW620 (EGF-R negative) and HCT-116 (EGFR strong) cell lines remained unresponsive. This combination was synergistic in HCT-8 and HT-29 cell lines while cetuximab induced no major modification of the IC50 of oxaliplatin in HCT-116 or SW620 cell lines. We then determined the effect of cetuximab on the EGF-induced EGFR phosphorylation and we highlight a correlation between the basal level of phospho-EGFR and the response to the combination. In vivo, the combination of cetuximab plus oxaliplatin significantly inhibited tumor growth of HCT-8 and HT-29 (tumor delay or Td = 21.6+/-2.9 and 18.0+/-2.9 days respectively, synergistic effect) compared to either oxaliplatin (Td=12.6+/-2.3 and 14.4+/-3.2 days respectively) or cetuximab (Td=13.4+/-2.9 and 14.5+/-2.4 days, respectively) alone in xenograft models. The combination had no effect on HCT-116 and SW-620 cell lines. The observed responses are strictly dependent on the cell type, and are not correlated with the level of EGFR expression but related to the basal level of phospho-EGFR. This study provides promising preclinical results for a possible clinical investigation of the combination of oxaliplatin plus cetuximab in chemorefractory colorectal tumors.