Phase I study of thoracic radiation dose escalation with concurrent chemotherapy for patients with limited small-cell lung cancer: Report of Radiation Therapy Oncology Group (RTOG) protocol 97-12

Purpose: The purpose of RTOG 97-12 was to determine the maximum tolerated dose (MTD) of thoracic radiation therapy (RT) with concurrent chemotherapy for patients with limited-stage small-cell lung cancer. Patients and Methods: Sixty-four patients received four cycles of cisplatin (60 mg/m² i.v.) and etoposide (120 mg/m² i.v. Days 1-3) (PE), with concurrent thoracic RT starting on Day 1. Thoracic RT was given during the first two cycles with 1.8 Gy/fraction daily to the clinical target volume, followed by thoracic RT to the gross tumor volume b.i.d. for the last 3, 5, 7, 9, or 11 treatment days (total dose 50.4, 54.0, 57.6, 61.2, or 64.8 Gy, respectively). The MTD was based on the dose that produced Grades 3-4 nonhematologic toxicity (mainly esophagitis and pneumonitis) in greater than 50% of patients. Results: After the first 8 patients were enrolled in Arm 1, administration of etoposide was changed from 120 mg/m² i.v. on Days 2 and 3 of each cycle to 240 mg/m² p.o. for patient convenience as outpatients. Total thoracic RT doses from 50.4 Gy to 61.2 Gy over 5 weeks given with PE were well tolerated. Three of the first 5 patients in the 64.8 Gy arm developed Grade 3 acute esophagitis; the MTD was determined to be 61.2 Gy. Fifty-four (87%) of the 62 evaluable patients achieved a complete (68%) or partial (19%) tumor response. The 18-month survival was 25% for patients receiving 50.4 Gy and 82% for those receiving 61.2 Gy. Conclusions: The MTD for this accelerated thoracic RT regimen with concurrent PE was 61.2 Gy over 5 weeks.