Chemoradiation paradigm for the treatment of lung cancer

For the treatment of advanced non-small-cell lung cancer, randomized controlled trials have shown that platinum-based chemotherapy and radiotherapy provide a measurable survival benefit compared with radiotherapy alone. Newer drugs that target growth factor receptors might further synergize with ionizing irradiation, although convincing data from multicenter phase III are currently lacking. The authors discuss why concurrent chemoradiation followed by consolidation platinum-based chemotherapy is an attractive approach for treating patients with inoperable tumors. 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. Key Points Based on data from multicenter phase III trials, combining platinum-based chemotherapy and radiotherapy to treat patients with locally advanced and inoperable NSCLC improves median and long-term survival Sequential administration of chemotherapy prior to radiotherapy compared with radiotherapy alone improves median as well as long-term survival by increasing systemic control Combining co