The superiority of combined-modality chemotherapy plus radiotherapy in a sequential fashion compared to radiotherapy alone has been shown in several other large randomized trials including a Radiation Therapy Oncology Group trial showing an improved 1-year and median survival with chemotherapy plus conventional radiotherapy compared to both conventional radiotherapy and hyperfractionated radiotherapy alone. A multicenter French study reported by Le Chevalier and associates also confirmed improved survival for the chemotherapy-plus-radiotherapy arm compared to radiotherapy alone (11% vs 5% 3-year survival, respectively) with an improved distant failure rate for chemotherapy plus radiotherapy (22% vs 46% at 1 year, respectively). Unfortunately, both treatment groups showed similarly high locoregional failure with 1-year local control rates of only 15% and 17%, illustrating the vexing problem of obtaining good locoregional control of disease in the locally advanced setting. Three meta-analyses reviewing > 50 trials have confirmed the survival benefit of combined platinum-based chemotherapy with radiotherapy over radiotherapy alone in locally advanced, unresectable lung cancer. canada-neighbor.com
The most recently published study was a large British trial randomizing 446 patients with localized, unresectable disease to two arms: (1) chemotherapy (mitomycin, ifosfamide, and cisplatin) followed by radical radiotherapy (median, 50 Gy; range, 40 to 60 Gy), or (2) radical radiotherapy alone (median, 50 Gy; range, 40 to 64 Gy). This trial allowed performance status (PS)-2 patients, and 15% of the chemoradiotherapy arm and 11% of the radiotherapy-only arm were PS-2 patients. The median survival and 2-year survival were not significantly different (p = 0.14) between the two arms: 11.7 months and 20% in the chemoradiotherapy arm, and 9.7 months and 16% in the radiotherapy arm. Inclusion of patients with poorer PS in this trial, unlike most other trials, is believed to have possibly influenced the results, particularly in the chemoradiotherapy arm.