Radiation and third-generation chemotherapy

Although platinum-based combination chemoradiation for locally advanced non-small cell lung cancer (NSCLC) has improved response rates and survival in large randomized trials and is now considered standard treatment, it is primarily offered to patients with good performance status who can tolerate aggressive, bimodality treatments. The results are better than treatment with radiotherapy alone but far from satisfactory, with local failure rates as high as 55% to 85% and average 5-year survival rates no better than 5% to 15%. Several new chemotherapeutic agents have shown independent activity against lung cancer, including taxanes (paclitaxel and docetaxel), vinorelbine, DNA topoisomerase I inhibitors (irinotecan and topotecan), and gemcitabine. With the advent of these third-generation chemotherapeutic agents, investigations using these new agents for combination chemoradiation are underway. Phase I/II combination chemoradiation studies using the third-generation agents offer new hope for improving therapeutic gain beyond that of platinum-based chemoradiation. In this article, the authors review preclinical and clinical results of chemoradiation treatments using the third-generation chemotherapeutic agents for inoperable stage III NSCLC.