In patients with advanced (stage IIIb/IV) NSCLC, the addition of cetuximab to chemotherapy has demonstrated increased activity compared with chemotherapy alone. Furthermore, the additio of cetuximab to RT in patients with locally advanced squamous cell head & neck carcinoma significantly prolongs the duration of locoregional control and median overall survival compared to radiotherapy alone. Therefore, the SCRATCH study was designed to assess the safety of synchronous cetuximab with radical RT in patients with Stage III NSCLC. The safety results of cohort 1 from this phase I study are presented below.Methods:
Twelve patients with inoperable stage III NSCLC were enrolled into cohort I. Inclusion criteria were performance status 0–1, adequate organ function, and disease encompassable within a radical RT volume. Exclusion criteria were previous malignancy, thoracic RT or treatment with EGFR (epidermal growth factor receptor) targeted therapy. Patients received platinum-based induction chemotherapy, followed by weekly intravenous cetuximab (initial dose 400mg/m2; maintenance dose 250mg/m2) and concomitant Rt (64Gy/32fractions/45days). The primary end-point was toxicity. NCI Common Toxicity Criteria (CTC) V3.0 assessments were preformed weekly during radiotherapy, and at regular follow-up visits.Results:
9 out of 12 patients coompleted the concomitant therapy as planned, with no dose reductions. 3 patients did not complete the full schedule. One died from bronchopneumonia mid-treatment; one experienced grade 3 lethargy following the first cetuximab dose and declined further cetuximab; one experienced a grade 2 skin reaction following the third dose of cetuximab and declined futher treatment. On follow-up only one patient has developed a grade III reaction – pneumonitis – which settled on steroids with intermittent oxygen. Three patients have died on follow-up (2 from disease progression and one from thromboembolic disease). Of the 12 patients entered ito the study, 8 have survived at least 1 year, measured from the first day of induction chemotherapy.Conclusion:
The results suggest that the early and late toxicities of synchronous cetuximab and radical RT are acceptable.