Randomized phase II trial comparing two schedules of thoracic radiotherapy (TRT) in limited disease small-cell lung cancer (LD SCLC).

Abstract

7027 Background: Concurrent chemotherapy and TRT is standard therapy for SCLC if all lesions can be included in a radiotherapy field (LD). Several schedules of TRT are used. One study showed that two fractions a day improved local control and overall survival (OS), but this schedule has not been compared to a commonly used 3 wks schedule. Methods: Eligible pts had LD SCLC and PS 0-2. Pleural fluid was accepted if negative cytology. Pts received 4 cycles of PE (cisplatin 75 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 q 3 wks) and were randomly assigned to 3 wks of 3D conformal TRT [A] 42 Gy (2.8 Gy x 1/day) or [B] 45 Gy (1.5 Gy x 2/day). TRT started 3-4 wks after the first PE. All responders received prophylactic cranial irradiation (PCI) 2 Gy x 15 ≤ 6 wks after last PE. Pts reported health related quality of life (HRQoL) on EORTC QLQ C30 + LC13. Primary endpoint: 1-year local failure. Secondary: OS, toxicity and HRQoL (dysphagia and dyspnea; a difference ≥ 10 points was considered significant). 75 pts were required in each arm to show a 30% improvement of local disease control with α=.05 and β=.8. Results: 159 eligible pts were enrolled at 18 sites in Norway May 05 – Jan 11 (A: 85, B: 74). Median age 60 (40-85); 52% men, 84 % PS 0-1, 11% pleural fluid. Mean no. of PE-cycles was 3.8, 97% completed TRT, 82 % PCI (no difference between arms). Response rates were similar (A: 92%, B: 94%; p=.8), but more pts on Arm B had CR (A: 13%, B: 35%; p=.01). There was no difference in local failure as first site of progression at 1 year (A: 17%, B: 12%; p=.4) or 1-year PFS (A: 44%, B: 50% ; p=.4). There was similar grade 3-4 esofagitis (A: 33%, B: 37 %; p=.7) and pneumonitis (A: 6 %, B: 7 %; p=.9). 2 pts (1 on each arm) died from pneumonitis. Pts in Arm B reported more dysphagia (A: 64 points, B: 73 points), but not more dyspnea (A: 29 points, B: 28 points). 1-year OS was similar (A: 77%, B: 76%; p=.9). Currently, 2-year survival among those followed ≥ 2 years (n=130) favors Arm B (A: 40%, B: 55%; p=.09) and so far (all pts followed ≥ 1-year; 103 events) median OS favors Arm B (A: 18.7 mos, B: 26.6 mos; p=.34). Conclusions: Twice daily TRT resulted in more CRs, slightly more dysphagia, similar 1-year local control and 1-year PFS. There are indications of improved 2-year and median OS in this arm.