Risk of severe radiation pneumonitis in gemcitabine (GEM) based consolidation chemotherapy after concurrent chemo-radiation (C-RT) in stage III non-small-cell lung cancer (NSCLC)

Abstract

17079 Background: Recent phase II study (S9504) showed that 3 cycles of consolidation docetaxel after C-RT is associated with prolonged survival but 6 pts (7%) had severe (≥gr 3) radiation pneumonitis and 2 (2.4%) died.(None at S9019) LCRG, a multinational Asian study group, designed a randomized phase II study aiming to assess the treatment outcomes of consolidation GEM or GEM/Carboplatin (CAR) after C-RT. GEM is a potent radiation sensitizer with known recall phenomena, thus we evaluated the risk of severe radiation pneumonitis with GEM-based consolidation chemotherapy after C-RT in this interim report. Methods: Enrollment criteria: Histologic proven NSCLC; attained CR/PR/SD after C-RT (Cisplatin-based chemotherapy between 25 mg/m2 and 40 mg/m2 per week or 60 mg/m2 to 100mg/m2 every 3 to 4 weeks; fraction dose not more than 2.0 Gy; total dose not less than 54 Gy and not higher than 64 Gy); ECOG PS 0–1; adequate hematologic/renal/liver function. Patients were screened for eligibility within 6 weeks after C-RT. Eligible patients are randomized to receive GEM 1250mg/m2 day 1,8 q21days with or without CAR 5XAUC day 1. Results: Between 3/04 and 9/05 we screened 51 patients and excluded 19. Six (31.5%) were excluded due to radiation pneumonitis.(gr 1=5 and gr 3 = 1). C-RT induced toxicity was the main reason for difficulty with accrual to this trial. We enrolled 32 patients (m:f 29:3; mean age 58 (40–78); adeno:scc:other 14:16:2; IIIa:IIIb 4:28) Median RT fraction and dose was 30 (27–32) and 60 Gy (54–64), respectively. 19 pts received GEM and 13 received GEM/CAR. Severe (≥gr 3) radiation pneumonitis was reported in 3 pts (9.3%) and 1 (3.1%) died from the complication. Another 10 and 6 pts had grade 1 and 2 radiation pneumonitis, respectively, but without significant clinical compromise. Conclusions: Radiation pneumonitis is common after C-RT with or without consolidation chemotherapy. However, severe radiation pneumonitis is relatively uncommon in pts who received GEM based consolidation chemotherapy after C-RT. A possible explanation is that we have screened out the high risk pts prior to enrollment. [Table: see text]