Concurrent chemotherapy with hyperfractionated accelerated thoracic irradiation in stage III non-small cell lung cancer

OBJECTIVES: We evaluated the effect of hyperfractionated accelerated radiotherapy combined with low dose radiosensitisers followed by standard dose chemotherapy in the treatment of unresectable stage III non small cell lung cancer (NSCLC). METHODS: Forty-seven patients received thoracic radiotherapy (1.5 bid x 5 days x 4 weeks) in combination with low dose daily (3-6 mg/m2) cisplatin +/- weekly vinblastine chemotherapy (step I), followed by three cycles of standard dose chemotherapy alone consisting of cisplatin (75-80 mg/m2) and vinblastine (8-16 mg/m2) given at 3-4 week intervals (step II). RESULTS: The overall response rate was 70% (21% CR). The progression free interval and the median survival duration were 10.4 months and 17.3 months, respectively. The 3 year survival rate was 21%. The site of first progression was local in 44%, distant in 41%, and simultaneous in 15% of patients. Levels of esophageal toxicity were significant but acceptable with the use of prophylactic therapy. Grade 3 or 4 esophageal toxicity was observed in 28 and 19% of patients during step I and II of the study, respectively. There were three deaths associated with esophageal toxicity. All occurred prior to the implementation of the prophylactic therapy for esophagitis. Acute pulmonary symptoms were reported in 25% of patients in step I, and pulmonary fibrosis, primarily asymptomatic, was observed in 51% of patients. Hematological toxicity was moderate. Two patients died of neutropenic sepsis/pneumonia. CONCLUSION: Concurrent chemotherapy and hyperfractionated accelerated radiotherapy followed by chemotherapy appears moderately effective in controlling tumour growth as measured by response rates and survival estimates. Toxicity is considerable but manageable and compatible with results from other combined modality studies.