Multicenter phase II trial of carboplatin (Cb) and gemcitabine (G) followed by concurrent chemoradiation in patients with unresectable stage III non-small-cell lung cancer (NSCLC): FEV1 as prognostic marker

Abstract

7558 Background: In patients (pts) with unresectable stage III NSCLC concurrent chemoradiotherapy (CRT) results in improved survival compared to sequential CRT, but comes at the cost of increased toxicity. Data from the recent HOG 01–24 trial suggest that survival of stage III NSCLC patients is correlated with the FEV1. Methods: Pts (PS 0–2) with unresectable stage III NSCLC and FEV1 ≥1.5L were treated with 3 cycles of induction chemotherapy (Cb AUC 5 on d1 and G 1,200 mg/m2 on d1 and d8 Q3 wks) followed by conventional radiotherapy (2.0 Gy/fraction, 5 fractions a week, up to a total dose of 60 Gy) with concurrent weekly cisplatin (Cis 30 mg/m2). The primary endpoint was overall survival at 2 years. An exploratory analysis the effect of FEV1 (expressed as % of predicted value) on survival was performed. Results: Between 02/2003 and 11/2005, 45 pts were enrolled. The demographics were as follows: 34/11 male/female, 14/31 stage IIIA/IIIB, median age 62 y (range 41–81 y), 31/12 FEV1 ≥70%/<70%, 42% squamous cell and 33% adenocarcinoma. All pts received at least 1 cycle CbG. CRT was started in 36 pts: median total radiation dose and duration was 60 Gy and 43 days. The overall response rate was 58% (2% CR, 56% PR). Primary grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (18%), febrile neutropenia (1%). No treatment-related deaths were observed. The median progression-free (PFS) and overall survival (OS) are 11.1 m and 20.4 m. The 1-, 2- and 3-yr OS rates are 62%, 38% and 17%. An FEV1 ≥70% was associated with a better survivall: median OS of 21.6 m vs 9.0 m and 2-yr OS of 48% vs 17% in pts with FEV1 ≥70% vs FEV1 <70% (HR 0.37; 95% CI 0.09 - 0.58). The HR (95%CI) was 1.10 (0.56 - 2.18) for PS 0–1 vs 2 and 0.92 (0.47 - 1.79) for stage IIIA vs IIIB. Conclusions: Induction chemotherapy with CbG followed by CRT with concurrent weekly Cis is well tolerated and results in promising overall survival in pts with unresectable stage III NSCLC. In these pts FEV1 appears to be a important prognostic marker. No significant financial relationships to disclose.