Paclitaxel, carboplatin and radiation therapy for non-small-cell lung cancer

Preclinically, the taxanes appear to potentiate radiation more effectively than do the platinum compounds. In our phase I trial (LUN-17) in patients with advanced non-small-cell lung cancer, we defined the maximum tolerated dose and toxicity profile of concomitant radiation and paclitaxel (Taxol). We then conducted a series of phase II clinical trials in patients with stage III A or stage III B non-small-cell lung cancer to explore the role of paclitaxel in a combined-modality approach; these trials were based on the very low paclitaxel concentrations needed to enhance radiation in the phase I trial and the relatively high response rate achieved. Our LUN-27 trial of weekly paclitaxel and concurrent radiation for 6 weeks with no adjuvant chemotherapy produced substantial response and survival rates with acceptable toxicity. LUN-56 added weekly carboplatin (Paraplatin) during the initial concurrent phase as well as two cycles of standard-dose paclitaxel and carboplatin. The ongoing LUN-63 phase II study delivers concurrent weekly paclitaxel and carboplatin with hyperfractionated radiation, followed by two cycles of adjuvant paclitaxel and carboplatin, to further improve local control and overall survival. We are currently extending the investigation of concurrent weekly paclitaxel plus radiation in a large-scale, three-arm, randomized phase II trial. To date, toxicity in all trials has been acceptable and compares favorably with other regimens. The major side effect, esophagitis, occurs predictably and is managed easily, abating shortly after therapy is completed. The rates of overall response and 1- and 2-year survival are very encouraging, and phase III evaluation is warranted.