DEVELOPMENT AND OPTIMIZATION OF ANTI-ANGIOGENIC TREATMENT OF LUNG CANCER

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Abstract

Anti-VEGF antibody bevacizumab has been approved for the treatment of non-small cell lung cancer (NSCLC) in Japan, and been mainly used as a first-line combination chemotherapy. Bevacizumab has already been established as one of the key drugs in the standard treatment of advanced NSCLC from the results of phase III trials. However, several issues exists concerning the indication of bevacizumab treatment such as (i) for patients with brain metastasis, (ii) for patients beyond PD, (iii) for elderly patients, (iv) combination chemotherapy with other molecular-targeted agents, (v) adjuvant or neoadjuvant settings, etc. On the other hands, VEGFR tyrosine kinase inhibitors (VEGFR-TKI), those have other molecular targets (i.e. PDGFR, FGFR, c-kit) and are called as ‘multi-target inhibitors’, have also promising profiles for NSCLC. The antitumor activities were observed both in single agents and in combination with other cytotoxic agents in the early phase of clinical trials. However, the results of phase III trials, those investigated the survival benefit of the combination of VEGFR-TKI and the platinum-doublet regimens over the conventional chemotherapies, were entirely disappointed. The development of VEGFR-TKI for NSCLC has come up to against a brick wall, and the developmental strategy should be changed dramatically. To optimize the anti-angiogenic treatment of NSCLC, the patient selection in clinical settings and the required clinical trials will be proposed in this session. Also, the developmental strategy of angiogenesis inhibitors will be discussed.

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