CLINICAL OUTCOMES AND FUTURE DIRECTION OF THE COMBINED RADIATION THERAPY AND MOLECULAR TARGETED DRUGS

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Abstract

Molecular target-based drugs combined with radiation therapy (RT) have been expected as promising approach in cancer treatment, and clinical trials using combined modalities have been carried out to evaluate the feasibility and efficacy of this approach. The main advantage of this approach is to improve local control without increase in the radiation-related toxic effects such as mucositis due to cancer-specific enhancement of radiosensitivity caused by molecular target-based drugs for radiosensitivity. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanisms underlying the interaction between radiation and molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting EGFR and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that RT combined with cetuximab, a specific monoclonal antibody for EGFR, resulted in improvement of overall and disease-specific survival rate compared with RT in locally advanced head and neck cancer. The median survival time was 49 months on the cetuximab plus RT versus 29.3 months observed in patients receiving RT alone. Regarding the toxic effects, the incidence of grade 3 or greater toxic effects did not differ significantly between the two groups, with the exception of acneiform rash and infusion reactions, In this symposium, established and potential molecular targets for potentiation of radiation-induced cell killing are summarized, especially focusing on EGFR and its signal transduction pathways; also clinical trials of combined RT plus molecular-target drug therapy are summarized to clarify the rationale and future direction of the combined RT and molecular-targeted drugs.

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