Concomitant weekly docetaxel, cisplatin and radiation therapy in locally advanced non-small cell lung cancer: A dose finding study

The optimal dose of weekly docetaxel in combination with cisplatin and concomitant thoracic radiation therapy (XRT) in patients with locally advanced non-small cell lung cancer (NSCLC) is not well defined. The purpose of this study was to define the maximal tolerated dose (MTD) of docetaxel in this combination. Eligible patients had unresectable stage IIIA or IIIB NSCLC without pleural effusion. Treatment consisted of cisplatin 25 mg/m² plus docetaxel weekly and concomitant standard XRT for a total of 60 Gy at 200 cGy/fraction/day 5 times weekly for 6 weeks. The starting dose of docetaxel in the first cohort was 15 mg/m²/week. This dose was escalated by 5 mg/m² per cohort of 3 patients. No intrapatient dose escalation was allowed. The doses of cisplatin and XRT were not escalated. A total of 23 patients were enrolled, and 19 patients were evaluable for analysis. The first cohort (docetaxel 15 mg/m²/week) completed treatment without any Grade 3 or 4 toxicities. The second cohort (docetaxel 20 mg/m²/week) was expanded to 6 patients because of Grade 3 cough observed in 1 patient. One of 5 patients experienced Grade 3 esophagitis at the docetaxel 25 mg/m²/week dose level. Dose limiting toxicity consisting of Grade 3 esophagitis was reached in 4 of 5 patients receiving docetaxel at 30 mg/m²/week. This study determined the MTD of weekly docetaxel to be 25 mg/m² when combined with cisplatin 25 mg/m² and radiation therapy for locally advanced NSCLC. Further evaluation of this regimen in a phase II trial is underway.