Phase II trial of up-front accelerated thoracic radiotherapy combined withchemotherapy and optional up-front prophylactic cranial irradiation in limited small-cell lung cancer

Purpose: To investigate the feasibility and outcome of bifractionated, up-f ront thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice dail y over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin an d etoposide) and optional low-dose, up-front prophylactic cranial irradiati on (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited sma ll-cell lung cancer. Patients and Methods: CT (etoposide 100 mg/m(2) for 3 days and cisplatin 25 mg/m(2) for 3 days) was started on day 8 or 15 after the first TR treatmen t. In the five subsequent cycles, cisplatin was given as a single 100-mg/m( 2) dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patien ts, and 2 in two patients. Thirty-six patients (69%) received the full plan ned six cycles of CT. Results: All treated patients were assessable for response. Thirty-one pati ents (60%) achieved a complete response, and 16 (30%) had a partial respons e. One-, 3- and 4-year survival rates were 74% (95% confidence interval [CI ], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), resp ectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patie nts experienced grade 3 or 4 acute toxicity. CT was well tolerated. Althoug h grade 3/4 neutropenia was observed in 86% of the patients, only 4% presen ted with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients, Conclusion: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long- term survival potential, J Clin Oncol 18:1662-1667, (C) 2000 by American Society of Clinical Oncolog y.