Induction chemotherapy followed by concurrent chemotherapy and definitive high-dose radiotherapy for patients with locally advanced non-small-cell lung cancer (stages IIIa/IIIb): a pilot phase I/II trial.

BACKGROUND: Overall prognosis of patients with locally advanced non-small-cell lung cancer (LAD-NSCLC) is still unfavourable. Different attempts to improve treatment results have been made using combinations of chemotherapy and radiotherapy. The aim of this pilot phase I/II investigation was to test the feasibility and toxicity of a definitive multimodality protocol in patients with irresectable NSCLC stages IIIA (N2) and IIIB. PATIENTS AND METHODS: Thirty LAD-NSCLC patients (stages IIIA/IIIB: 3/27; median age: 54 years, range 34-70; male/female: 17/13) who were consecutively enrolled onto our ongoing neoadjuvant multimodality protocol from October 1996 to February 1999 remained inoperable after induction treatment. Three cycles of cisplatin/etoposide (PE) were followed by hyperfractionated accelerated radiotherapy (HF-RTx: 1.5 Gy bid up to a total dose of 45 Gy in 3 weeks) concurrent with one cycle of PE. Definitive local treatment was completed with a small volume boost of 20 Gy (qd), adding up to a total dose of 65 Gy to the primary. Patients were routinely offered prophylactic cranial irradiation (PCI; 30 Gy; 2 Gy qd).
RESULTS: Overall toxicity of the definitive CTx/RTx protocol-the main endpoint of this investigation-turned out to be acceptable (oesophagitis grade 3/4: 6/4 patients; pneumonitis grade 3/4: 0/1 patients; no treatment-related deaths). Actuarial survival at 2 years was 31% with a loco-regional control rate of 21%.
CONCLUSIONS: This regimen turned out to be feasible with acceptable toxicity and will serve as a reference arm in a planned randomised trial in stage IIIB NSCLC, testing the value of surgery in this setting: preoperative induction CTx/RTx followed by surgery versus definitive CTx/RTx.

RCT Entities:   Population Interventions Outcomes