Paradigms in chemoradiotherapy

Abstract

The efficacy of radiation in locally advanced non- small cell lung cancer (NSCLC) is limited. In a search for improving the outcome, particular attention has focused on the possibility of combining radi- ation with chemotherapy. The two most frequently used combined modality strategies include induction chemotherapy (chemotherapy preceding radiation) and concurrent chemoradiation. The former allows for drug delivery in full doses and in principle aims at a reduction of micrometastatic disease, whereas the latter is believed to improve locoregional control by making tumour cells more vulnerable to radiotherapy. The results of phase III trials of induction chemo- therapy were equivocal; nevertheless, three large trials using platinum-based regimens demonstrated significant survival benefit. The role of single agent platinum compounds (believed to be radiosensitising agents) applied concurrently with radiotherapy is controversial. Improved survival with this strategy was demonstrated in two studies, but several other studies were negative. Concurrent application of multidrug platinum-based chemotherapy in conventional sched- ules has been found relatively toxic yet feasible in selected patients. The direct comparison of sequential versus concurrent use of chemotherapy and radiation demonstrated the superiority of the latter, but at the expense of higher acute in-field toxicity. More recently, several new agents, including taxanes, vinorelbine and gemcitabine, have appeared promising in NSCLC. Their role in combined modality regimens warrants further clinical research. Chemotherapy as an adjunct to radiation has become a standard in fit patients with locally advanced NSCLC. The gain from the combined modality approach, however, is modest on average and should be weighted against increased early and late toxicity. Further studies built upon recent positive results should focus on identifying the means of optimal interactions between the two modalities. This research should define the most effective types and doses of anti-cancer agents as well as the optimal features of radiotherapy. Additionally, the knowledge of the biological characteristics of individual tumours, in particular their expected response to therapy, may contribute to further progress.