Phase I trial of outpatient weekly docetaxel, carboplatin and concurrent thoracic radiation therapy for stage III unresectable non-small-cell lung cancer: A Vanderbilt cancer center affiliate network (VCCAN) trial

Purpose: Docetaxel, an active agent for non-small cell lung cancer (NSCLC), has demonstrated activity as a radiosensitizer in numerous pre-clinical studies. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly Docetaxel, Carboplatin with concurrent thoracic radiation therapy (TRT) in patients with unresectable stage III NSCLC. Patients and methods: In this phase I clinical trial, Docetaxel was administered weekly as a 1-h intravenous infusion for 6 weeks with a starting dose of 20 mg/m². Docetaxel doses were escalated by 10 mg/m² increments in successive cohorts of three patients. DLT was defined as grade ≥3 nonhematologic and hematologic toxicity according to RTOG toxicity criteria. Once the DLT of Docetaxel alone was reached, weekly Carboplatin (AUC 2) was added at a DLT-2 dose of Docetaxel (two dose levels below that of dose limiting toxicity). Docetaxel doses were again escalated at 10 mg/m² increments in successive cohorts of three new patients to define further DLT and MTD of Docetaxel/Carboplatin with TRT. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). Results: Fifteen patients were entered onto this study with Docetaxel alone through three dose escalations (from 20 to 40 mg/m² weekly). The DLT of weekly Docetaxel/TRT was esophagitis and the MTD was 30 mg/m² per week for 6 weeks. Nine more patients were added with the Docetaxel/Carboplatin/TRT regimen. The DLT of weekly Docetaxel/Carboplatin with TRT was esophagitis and the MTD of Docetaxel was 20 mg/m² per week with weekly Carboplatin (AUC 2). There were 2 complete responses and 13 partial responses in 25 evaluable patients (RR 60%). Conclusions: This combination regimen has activity with manageable toxicity in patients with stage III NSCLC. A phase II study is planned to define activity.