Phase I study of concurrent high-dose three-dimensional conformal radiotherapy with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small-cell lung cancer.

PURPOSE: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Eligible patients with unresectable Stage III NSCLC, age ≥ 20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V(20)) ≤ 30% received three to four cycles of cisplatin (80 mg/m(2) Day 1) and vinorelbine (20 mg/m(2) Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively.

RESULTS: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V(20) >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively.

CONCLUSIONS: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.