Abstract
Purpose/Objective: Concurrent chemo-radiation (CRT) is the treatment of choice for local advanced NSCLC patients. Despite the curative intent of the treatment, survival is poor with a median survival of about 16-18 months (m) and a 5 year (y) survival of 15%. The loco-regional control rate at 2 y is only about 30% in clinical trials. This randomized phase-II trial tested a dose intense oral vinorelbine (Nav) regimen with two doses of RT, 60 Gy/30 F (arm A) and 66 Gy/33 F (arm B). Materials and Methods: Before randomization to arm A or B, the patients were treated with 2 cycles of induction chemotherapy (Carboplatin+Nav). In both arms, Nav was given as concurrent chemotherapy (a fixed dose of 50 mg 3/week for the full course of CRT). Follow-up CT-scans were performed every 3 m starting 1 m after commencing radiotherapy for 2 y and then every 6 m. As part of the protocol, a PET-CT scan was conducted 9 m after randomization. The primary endpoint was the Local Progression Free Survival Rate (LPFSR). The goal of the study was within the 95% confidence interval (95%CI) to have a LPFSR at 9 m of 80%. Log rank tests were used to test survival. Results: In arm A and B, 59 and 58 patients were eligible. The two arms were well balanced. The minimum and median potential follow-up was 14.5 and 32.6 m, respectively. The median number of Nav was 18 x in arm A and 20 x in arm B. Of the patients, 10% had 20%). A late effect esophageal stricture/ulceration G3 or more occurred in 3 (5%) of the patients in arm A and 4 (7%) in arm B, and one of these in arm B was a G5 fistula at the site of the primary tumor. Conclusions: The phase II goal was not met in neither of the treatment arms. This may be caused by the extensive use of PET-CT scan in the study revealing progressions earlier than was expected from previous studies, or it could have been caused by the omission of concurrent cisplatin. The survival of the two arms was however comparable. Since both treatment arms were well tolerated with no differences in toxicity between the arms, and the 66 Gy arm had a trend to better loco-regional control, we have chosen this treatment arm (with cisplatin added) as the reference arm in a phase III (Figure Presented).