Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: Radiation Therapy Oncology Group Protocol 91-06

Purpose: Patients with locally advanced inoperable non-small-cell lung cancer (NSCLC) have a poor clinical outcome. We conducted a prospective study to evaluate the merit of chemotherapy administered concurrently with hyperfractionated thoracic radiation therapy. Patients and Methods: Seventy- nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg twice daily) on days I to 14 of a 28-day cycle (75 mg/d if body-surface area [BSA] < 1.70 m²), intravenous cisplatin 50 mg/m² on days I and 8, and hyperfractionated radiation therapy 5 days per week (1.2 Gy twice daily > 6 hours apart; total, 69.6 Gy). Results: Seventy- six assessable patients with a Karnofsky performance status ≥ 60 and adequate organ function who had received no prior therapy were evaluated for clinical outcome and toxic effects. After a minimum follow-up duration of 21 months, the 1 - and 2-year survival rates and median survival duration were 67%, 35%, and 18.9 months overall; they were 70%, 42%, and 21.1 months for patients with weight loss of ≤ 5%. Toxicity was significant; 57% developed grade 4 hematologic toxicity, 53% grade 3 or 4 esophagitis, and 25% grade 3 or 4 lung toxicity. However, only 6.6% of patients had grade 4 or lethal nonhematologic toxicity, which included three treatment-related deaths (two of pneumonitis and one of renal failure). Conclusion: Concurrent chemoradiation therapy with oral etoposide and cisplatin plus hyperfractionated radiation therapy is feasible. The survival outcome from this regimen compares favorably with that of other chemoradiation trials and even of multimodality trials that have included surgery.