Patients with WHO performance status 0–2 histologically confirmed, inoperable, stage I–III non-small cell lung cancer were recruited into an open phase I dose escalation trial. Three cohorts of six patients were recruited sequentially. Total dose was escalated from standard CHART radiotherapy of 54 Gy/36f/12 days to 57.6 Gy (2 × 1.8 Gy fractions on day 15, Group 1), 61.2 Gy (4 × 1.8 Gy fractions on days 15–16, Group 2) and 64.8 Gy (6 × 1.8 Gy fractions on days 15–17, Group 3).
Between April 2010 and May 2012, 18 patients were enrolled from 5 UK centres and received escalated dose radiotherapy. 14 were male, 16 squamous cell histology and 12 were stage IIIA or IIIB. The median age was 70 years and baseline characteristics were similar across the three dose cohorts. One patient did not start escalated radiotherapy but all remaining patients completed their planned radiotherapy schedules. Of these 9 patients have died to date with a median survival of 2 years across the three cohorts. Grade 3 or 4 adverse events (fatigue, dysphagia, nausea and anorexia – classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) were reported in 6 patients but the pre-specified dose limiting toxicities (grade 4 early oesophagitis; grade 3 cardiac, spinal cord and pneumonitis) were not observed.
CHART remains a radiotherapy schedule in routine use across the UK and in this dose escalation study no dose limiting toxicities were observed. We feel the dose of 64.8 Gy/42f/17 days should be taken forward into further clinical trials. The sample size used in this study was small so we plan a randomised phase II study that includes other radiotherapy schedules to confirm safety and select an accelerated sequential chemo-radiotherapy schedule to take into phase III studies.