Chemoradiation paradigm for the treatment of lung cancer

For the treatment of locoregional advanced stage III non-small-cell lung cancer, when chemotherapy is added sequentially to radiotherapy it acts systemically and is aimed at reducing distant metastases. Concurrent chemotherapy and radiation, however, is intended to enhance the locoregional efficacy of this modality. Combined effects of these modalities are based on their different toxicity profiles, leading to a reduced toxicity : efficacy ratio of the combination. Controlled trials investigating this additive approach indicate that concurrent application of chemotherapy and radiotherapy results in a small but significant benefit for locoregional control, which translates into a small but measurable survival benefit. This benefit is most evident when looking at 3-year or 5-year overall survival rates, when it is of clinical significance. The use of single-agent cisplatin has already demonstrated major radiosensitizing effects whereas the radiosensitizing properties of concurrent application of the single-agent carboplatin have not been observed in controlled trials. Newer drugs such as vinorelbine, the taxanes and gemcitabine might enhance this effect, although no improvement has been observed in randomized controlled trials comparing such regimens with single-agent cisplatin. New 'targeted' agents might synergize with ionizing irradiation and provide an interesting rationale concerning combined modality therapy, but this hypothesis awaits prospective clinical evidence from randomized controlled trials.