Dose-escalation study of chemoradiotherapy of three-dimensional conformal radiotherapy (3D-CRT) with accelerated hyperfractionation (AHF) and concurrent chemotherapy (cisplatin and vinorelbine) for unresectable stage III non-small cell lung cancer (NSCLC).

Abstract

e17518 Background: To determine a recommended dose (RD) of radiotherapy using AHF for unresectable NSCLC. Methods: Eligible patients had unresectable stage III NSCLC, age of less than 75 years, PS: 0 or 1, V20 of 35% or less. PET was used for staging. Cisplatin (80mg/m2) was administered on day 1 and vinorelbine (20mg/m2) was administered on days 1 and 8 for first cycle. Twice-daily 3D-CRT (1.5 Gy per fraction) without elective nodal irradiation started on day 1. Total doses were 60 Gy in 40 fractions and 66 Gy in 44 fractions at levels 1 and 2 respectively. After concurrent chemoradiotherapy, consolidation chemotherapy regimen was cisplatin (80mg/m2) on day 1 and vinorelbine (20mg/m2) on days 1 and 8 every 4 week for three cycles. The dose-limiting toxicity (DLT) was defined as grade ≥a3 esophagitis, grade 3 neutropenic fever, grade ≥a3 other non-hematologic toxicities and interruption of irradiation for more than 2 weeks. DLT was monitored for 90 days. Results: A total of 12 patients were enrolled (n=6,4 in the levels 1,2). DLTs were noted in 2 patients at Level 1,which were grade 3 esophagitis and the other grade 3 febrile neutropenia. Radiation dose was escalated up to 66 Gy in 44 fractions (Level 2), and there was no DLT in level 2. In principle, Sixty-six Gy in 44 fractions (Level 2) should be the RD. Major toxicities were leucopenia, neutropenia, and anemia. The response rate (RR) and 1-year survival rate was 83.3% and 91.7%, respectively. The progression free survival time was 11.3 months. Conclusions: The RD was 66 Gy in 44 fractions (Level 2). The toxicity of this chemoradiothrapy regimen was managiable and efficacy is promissing. Phase II study is warranted.