Phase I study of concurrent high-dose three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC)

Abstract

7546 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. Methods: Eligible patients (unresectable stage III NSCLC, age ≥ 20 years, PS 0–1, V20 ≤ 30%) received cisplatin (80mg/m2 day 1) and vinorelbine (20mg/m2 days 1 and 8) repeated every 4 weeks for 3–4 cycles. The dose of 3D-CRT was 66 Gy in 33 fractions, 72 Gy in 36 fractions, and 78 Gy in 39 fractions at levels 1–3, respectively. The dose-limiting toxicity (DLT), defined as grade ≥3 esophagitis, pneumonitis, myelitis, dermatitis and heart injury, and early stop of protocol treatment, was evaluated in 6–12 patients at each level. Results: Of the 17, 16 and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled into levels 1–3, respectively, of the study. A total of 26 patients were excluded because of V20 > 30% (n=10), overdose to the esophagus (n=8) and brachial plexus (n=2), comorbidity (n=3), or patient refusal (n=3). There were 26 men and 5 women with a median (range) age of 60 (41–75) years. Of these, 23 (74%) had adenocarcinoma and 20 (65%) had stage IIIA disease. The full planned dose of radiotherapy could be administered in all the patients, and more than 80% of the patients received 3–4 cycles of chemotherapy. 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 one, two and one patients, respectively. DLT was noted in 17% of the patients at each level. Two (6%) complete and 27 (87%) partial responses were obtained. In a preliminary survival analysis, the median progression-free and overall survivals were determined to be 15.0 months and 37.6 months, respectively. Conclusions: At the level of 78Gy, only 25% of the patients assessed for eligibility were actually eligible. Toxicity was relatively mild up to 78 Gy in this highly selective patient group. Thus, we determined that the recommended dose of 3D-CRT administered concurrently with cisplatin and vinorelbine chemotherapy was 72Gy. [Table: see text]