Concurrent chemotherapy (CT) and radiotherapy (RT) in locally advanced non-small cell lung cancer (NSCLC): a review

Stage III or locally advanced non-metastatic, non-small cell lung cancers comprise about 40% of all NSCLC. A proportion of patients with Stage III NSCLC can be treated by induction RT/CT followed by surgery, but the majority, in particular all Stage IIIB, are not candidates for this approach. For these patients, RT alone is generally considered as the standard treatment. RT has a modest, but definitive curative potential, with 1-, 2-, and 5-year survivals of about 40%, 20% and 5%, respectively, and median survival of 9-12 months. Combination CT-RT, depending on its type and rationale, is aimed at improving survival via a decrease of local or distant failure rates or both. Combined modality (CM) can be subdivided into 3 categories: sequential, concomitant and alternated regimes. Concomitant and alternated CT-RT have some common characteristics and rationale, the overall time playing a central role. This paper reviews studies of inoperable NSCLC treated with these CM, excluding sequential CT-RT trials, which would require a separate discussion. Numerous Phase I-II studies have been recently published on concomitant or alternated schemes and 33 of them are presented in this paper. Although it is hazardous to readily compare their results with those of RT-alone studies, several trials using platin-based combination chemotherapy, concurrently or alternated with RT, have shown impressive response rates and encouraging survivals, at a price of significant toxicity. Seven randomized trials comparing RT alone versus concomitant CT-RT are now available: the 3 non-cisplatin trials have failed to show any improvement in survival with CM, whereas among the 4 cisplatin trials, only one demonstrated a benefit with low-dose cisplatin added to RT. Implications for future clinical research will be discussed.