Dose-escalation with CHARTWEL (continuous hyperfractionated accelerated radiotherapy week-end less) combined with neo-adjuvant chemotherapy in the treatment of locally advanced non-small cell lung cancer.

Abstract

a radiation-dose-escalation study was undertaken to assess the therapeutic benefit of combining accelerated hyperfractionated radiotherapy (RT) with neo-adjuvant chemotherapy (CT) in non-small-cell lung cancer (NSCLC). One hundred and thirteen patients with locally advanced NSCLC were entered into a phase II trial of CHARTWEL (CHART Week-End-Less) 54 Gy or 60 Gy with or without three cycles of CT. Acute oesophageal reactions and analgesia were scored for up to 8 weeks after the start of RT. Pneumonitis, lung fibrosis, spinal cord and oesophageal strictures, were assessed using clinical and radiological criteria from 3 months onwards and throughout the study. Haematological and gastrointestinal toxicity was monitored in those patients undergoing CT. Endpoints for treatment outcome were overall survival, disease-free survival and loco-regional control. Chemotherapy enhanced the incidence and duration of acute dysphagia,but the increase was transient. Healing occurred in all cases and there has been no evidence of long-term oesophageal complications. Clinically, almost 25% of those receiving CT+RT had Grade 2 pneumonitis, higher than seen with RT alone. However, the 1 patient with severe Grade 3 pneumonitis was in the RT 60 Gy alone group. An incidence of 17% Grade 2 pulmonary fibrosis at 2 years was seen with CT, slightly lower than with RT alone. To date, there is no evidence of Grade 3 lung fibrosis. There was a higher scoring of lung damage with the radiological endpoint, which gave no indication that CT increased pulmonary toxicity over that of RT alone. Loco-regional control at 2 years was 37% and 55% for CHARTWEL 54 Gy and 60 Gy alone compared with 72% in those treated with 60 Gy and neo-adjuvant CT However, this did not translate into a survival advantage. This study of CHARTWEL combined with induction chemotherapy, has shown that the strategy is feasible and that a possible therapeutic benefit may be obtained by the addition of CT. Although neo-adjuvant treatment increased acute mucosal reactions and slight-to-moderate pneumonitis seen with CHARTWEL 60 Gy, the clinical management and quality of life of these patients is similar to those treated with radiotherapy alone.