SOCCAR: A randomised phase II trial comparing sequential versus concurrent chemotherapy and radical hypofractionated radiotherapy in patients with inoperable stage III Non-Small Cell Lung Cancer and good performance status

Background: Cure of lung cancer is impossible without local tumour control. This can be compromised by accelerated repopulation of tumour cells during radiotherapy and chemotherapy. A strategy to minimise accelerated repopulation might improve local control. We investigated whether concurrent chemo-radiotherapy could be given safely over four weeks. Methods: We conducted a randomised phase II trial in which patients with inoperable Stage III Non-Small Cell Lung Cancer (NSCLC) received a radical radiation dose over four weeks rather than conventional fractionation. Treatment was given either sequentially or concurrently with three to four cycles of cisplatinum and vinorelbine. 130 patients with inoperable stage III NSCLC and PS 0-1 were randomised to receive cisplatinum and vinorelbine with either sequential or concurrent chemo-radiation using 55 Gy in 20 fractions over four weeks. The primary end-point was treatment related mortality. Secondary end-points were toxicity and survival. Findings: Treatment related mortality was: 2.9% (exact 95% confidence interval [CI] 0.36-10.2%) and 1.7% (exact 95% CI 0.043-9.1%) for the Concurrent and Sequential group respectively; relative risk (RR) 1.25; (95% CI 0.55, 2.84). Toxicity was similar between arms; grade 3 or worse oesophagitis was 8.8% versus 8.5%; RR 1.02 (95% CI 0.58, 1.79). OS HR was 0.92; 95% CI (0.60-1.39; p = 0.682). The 2 year overall survival rates were: 50% versus 46%; RR 1.06 (95% CI 0.77, 1.46) for Concurrent versus Sequential. Interpretation: A strategy to minimise the effects of accelerated repopulation using accelerated hypofractionated radiotherapy with chemotherapy is feasible, and reasonably safe for patients with stage III NSCLC. The reported two year survival is promising and suggests that a four week regime of radiotherapy should be compared with conventionally fractionated radiotherapy in an adequately powered randomised controlled phase III trial. (C) 2014 Published by Elsevier Ltd.