Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial

Objectives: The non-small cell lung cancer (NSCLC) meta-analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery. radical radiotherapy or 'best supportive care'. However, it included many small trials and trials with differing eligibility criteria and chemotherapy regimens. The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta-analysis. Methods: In the surgery setting, a total of 381 patients were randomised to chemotherapy (C, 192 patients) or no chemotherapy (NoC, 189 patients). C was three 3-weekly cycles of cisplatin/vindesine, mitomycin/ifosfamide/cisplatin, mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin. Results: Chemotherapy was given before surgery in 3% of patients whilst 97% received adjuvant chemotherapy. Baseline characteristics were: median age 61 years, 69% male, 48% squamous cell, 93% WHO PS 0-1, 27% stage I, 38% stage II, and 34% stage III. Complete resection was achieved in approximately 95% of patients. In the C group, 13% received no chemotherapy, 21% one or two cycles, and 64% all three cycles of their prescribed chemotherapy (60% of the latter with no delays or modification). 30% had grade 3/4 toxicity, mainly haematological, nausea/vomiting and neutropenic fever, and six patients were reported as having a treatment-related death. 198 (52%) of patients have died, but there is currently no evidence of a benefit in overall survival to the C group: HR 1.02 (95% CI 0.77-1.35), P = 0.90). Conclusions: This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I-III NSCLC. However, the hazard ratio and 95% confidence intervals are consistent with the previously reported meta-analysis and two large recently reported trials, which suggest a small survival benefit with cisplatin-based chemotherapy. (C) 2004 Elsevier B.V. All rights reserved.