Phase I study of concurrent real-time tumor-tracking thoracic radiation therapy with paclitaxel and carboplatin in locally advanced non-small cell lung cancer.

INTRODUCTION Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT). PATIENTS AND METHODS Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m(2) followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5mg/m(2) per level. RESULTS Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m(2) and 45 mg/m(2)), carboplatin (AUC=2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m(2) and carboplatin, AUC=2). At Level 2 (paclitaxel, 45 mg/m(2) and carboplatin, AUC=2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m(2) and 40 mg/m(2), respectively. CONCLUSIONS This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m(2) at AUC=2, respectively. Further studies are warranted to evaluate the efficacy of this regimen.