Phase II Trial of Concurrent Paclitaxel, Carboplatin, and External-Beam Radiation Followed by Surgical Resection in Locally Advanced Non–Small-Cell Lung Cancer, Protocol 99-444

PurposeWe conducted a phase II study to evaluate the utility and outcomes of concurrent weekly lowdose chemotherapy with concurrent radiation in an effort to “downstage” patients with locally advanced non–small-cell lung cancer (NSCLC).Patients and MethodsEighteen patients with pathologically confirmed stage IIIA (T1-3 N2 or T3 N1) and 3 patients with stage IIB (T3 N0) NSCLC were enrolled. Seventeen of 18 patients with stage IIIA cancer had N2 disease. A chemotherapy/radiation schedule consisted of paclitaxel 50 mg/m² and carboplatin administered at an area under the curve of 2 weekly for 5 weeks along with chest irradiation of 45 Gy. Patients with regressed or stable disease upon restaging were considered surgical candidates. Patients deemed inoperable were given additional radiation therapy.ResultsTwenty-one patients were enrolled from April 2000 to March 2004. Data from 21 patients were available for evaluation at the time of analysis. Grade 3/4 constitutional and pulmonary toxicity was ≤ 10%. Grade 3/4 lymphopenia was noted in 9.5% of patients. One treatment-related death from postoperative acute respiratory distress syndrome occurred. Seventeen of 21 patients completed neoadjuvant therapy and 15 patients underwent resection. Four of 15 patients had a complete histopathologic response at the time of resection. Followup data were available on 20 patients. Overall, the median progression-free survival was 14.1 months. The median overall survival was 26.1 months. Six of 20 patients remain relapse free (range, 19.3-70.8 months).ConclusionNeoadjuvant low-dose weekly chemotherapy given concurrently with conventional chest irradiation might improve outcomes in patients with stage IIB and IIIA NSCLC with acceptable toxicity.