Abstract
Lung cancer is the leading cause of cancer-related deaths in industrialized countries and non small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cisplatin doublet based chemotherapy, which is the recommended regimen in first line therapy in advanced or metastatic NSCLC, improves survival but in low proportion. Monoclonal antibodies (mAbs) are a novel promising therapeutic class used with great results in inflammatory diseases such as rheumatoid arthritis. Antibodies are natural proteins with modular structure, specific pharmacodynamics and pharmacokinetics and possibly produced against any antigens, thus giving them several advantages over small drug therapeutics. In solid tumors, therapeutic mAbs improved progression free survival (PFS) and overall survival (OS) of patients with breast and colon cancers and had considerably changed the treatment in clinical practice. In NSCLC, bevacizumab, an anti-VEGF mAb, and cetuximab, an anti-EGFR mAb, are the most studied antibodies. Bevacizumab acts on angiognenesis and improved PFS of non squamous NSCLC but in low proportion as shown in two large phase III trials. It was approved by European Medicines Agency (EMEA) and Food and Drug administration (FDA) as a first line therapy in combination with cisplatin doublet chemotherapy. Cetuximab slightly enhanced OS but did not improve PFS in two large phase III trials. These results added to high adverse effect lead to cetuximab refusal by EMEA and FDA in NSCLC. At first glance, the results of mAbs in NSCLC are somewhat disappointing, in contrast to the benefits obtained with mAb treatments in other solid tumors. However, many other mAbs directed against novel targets, such as IGF1-R or CTLA-4, and new mAbs targeting VEGFR and EGFR pathways with different pharmacodymamical and pharmacokinetic properties are under evaluation and may change our vision of taking care of patients with NSCLC. In conclusion, it seems that mAbs therapy in NSCLC clearly marks the start of a new era in NSCLC treatment, with promises in improving patient survival and quality of life.
Highlights
Cytotoxic agents and radiation therapy have been used to improve the survival and quality of life of patients with cancer, but they no longer increase patient survival and yield many side effects
A phase III trial is in progress to compare carpolatin/ paclitaxel followed by radiotherapy plus cetuximab and concurrent chemotherapy followed by radiotherapy in locally advanced non small cell lung cancer (NSCLC)
We previously showed that aerosolized cetuximab passed slowly and poorly in blood in mice [103]
Summary
Cytotoxic agents and radiation therapy have been used to improve the survival and quality of life of patients with cancer, but they no longer increase patient survival and yield many side effects. Antibodies have become major biodrugs for treating solid and hematological tumors They are natural proteins that bind to one of a huge variety of molecular targets with great specificity. Therapeutic mAbs are specific, they have pharmacodynamical and pharmacokinetic advantages over small molecule drugs, together with limited toxicity. Treatment with mAbs has greatly prolonged the survival of patients with solid tumors like breast and colon cancers [4,5]. They are providing hope to patients with metastatic or locally advanced NSCLC who cannot be treated by surgery.
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