Report of phase ii trial of concurrent chemoradiotherapy with radical thoracic irradiation (60 gy), infusional fluorouracil, bolus cisplatin and etoposide for clinical stage IIIB and bulky iiia non-small cell lung cancer

Purpose: To assess the response rate, median and long-term survival of patients (pts) with locally advanced, initially inoperable non-small cell lung cancer (NSCLC) treated on a phase II study of radical thoracic radiotherapy (TRT) and concurrent radiosensitizing chemotherapy. Methods and Materials: From 3/87 to 7/90, 41 previously untreated patients at Fox Chase Cancer Center with locally advanced non-small cell lung cancer, 24 with bulky clinical Stage IIIA, and 17 with IIIB disease, received concurrent thoracic radiotherapy (60 Gy/2.0 Gy/d in 6 weeks) and 2 cycles of infusional 5FU (640-800 mg/m²/24 hrs × 5 d); cisplatin (20 mg/m² qd × 5); and etoposide (50 mg/m² d 1, 2, 5) administered days 1 and 28 of TRT. Results: Forty of 41 were evaluable. Response rate was 90%, with radiographic CR in 20%. Thirteen pts (33%) underwent thoracotomy and complete resection with clinical downstaging in 10, including three pathologic CR's. Overall median survival was 14 months and 2-year survival was 38% with no difference between CS IIIA and IIIB pts (p = 0.2224). At median potential follow-up of 42 months, 8/40 pts. (20%) are alive and progression-free, including 4 of 13 resected pts. The chief toxicity was esophagitis, occurring in 32 pts. (80%), Grade 3-4 in 21 (52%), with 13 (33%) requiring hospitalization and 7 (18%) needing TPN. Grade 3-4 granulocytopenia was noted in 20 pts. (50%) with ten episodes of fever mandating intravenous antibiotics. Cardiac ischemia was documented in 2 (5%). Of 13 thoracotomy pts, six underwent lobectomy without perioperative mortality; 3 of 7 pneumonectomy pts died post-operatively, two from broncopleural fistula, and one from ARDS. Conclusion: This aggressive regimen produced a 2-year survival (38%) comparable to the best arm of cancer and leukemia groups B study 8433, which administered radical thoracic radiotherapy after protoadjuvant vinblastine and cisplatin in similar and earlier stage non-small cell lung cancer patients. Toxicity, particularly esophagitis, was severe, but of short duration. An unacceptably high complication rate was seen following pneumonectomy, but not lobectomy.