Background Concurrent chemotherapy plus radiation therapy (chemoRT) is the standard treatment for stage IIIA(N2) non-small cell lung cancer (NSCLC), a common disease entity. Phase II studies demonstrated feasibility of resection after chemoRT with encouraging survival rates. This phase III trial compared both approaches. Methods Patients with stage T1-3pN2M0 NSCLC were randomized before induction chemoRT (2 cycles of cisplatin and etoposide [PE] concurrent with 45 Gy RT). If no progression, arm 1 underwent resection, and arm 2 continued RT uninterrupted to 61 Gy. Two additional cycles of PE were given. The primary endpoint was overall survival (OS). Findings Progression-free survival for 396 eligible patients was superior in arm 1: median 12.8 versus 10.5 months, p=0.017, hazard ratio (HR) 0.77 (0.62,0.96); 5-yr 22.4% versus 11.1%. Median OS was 23.6 versus 22.2 months, p=0.24, HR 0.87 (0.70,1.10). Five-year survivals were arm 1, 27.2% and arm 2, 20.3%; odds ratio 0.63 (0.36,1.10, p=0.10). N0 status at thoracotomy predicted median OS of 33.5 months (5-year, 41.8%). Major chemoRT toxicities were neutropenia and esophagitis. Treatment-related death occurred in 16 (7.9%) patients on arm 1, of which 14 were post-pneumonectomy; and in 4 (2.1%) on arm 2. An exploratory analysis showed improved OS for patients who underwent lobectomy versus a matched cohort on chemoRT alone, but not for those undergoing pneumonectomy (matched similarly). Interpretation There was no significant survival advantage to surgery after chemoRT, despite improved PFS. Both chemoRT with definitive RT and chemoRT followed by resection (preferably lobectomy) are options for patients with stage IIIA(N2) NSCLC.

A B S T R A C T PurposeAdjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC) is now accepted on the basis of several randomized clinical trials (RCTs) that demonstrated improved survival. Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB disease is unclear. This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC. Patients and MethodsWithin 4 to 8 weeks of resection, patients were randomly assigned to adjuvant chemotherapy or observation. Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy. Chemotherapy consisted of paclitaxel 200 mg/m 2 intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was overall survival. ResultsThree hundred-forty-four patients were randomly assigned. Median follow-up was 74 months. Groups were well-balanced with regard to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were the predominant toxicity; there were no treatment-related deaths. Survival was not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P ϭ .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors Ն 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P ϭ .043). ConclusionBecause a significant survival advantage was not observed across the entire cohort, adjuvant chemotherapy should not be considered standard care in stage IB NSCLC. Given the magnitude of observed survival differences, CALGB 9633 was underpowered to detect small but clinically meaningful improvements. A statistically significant survival advantage for patients who had tumors Ն 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.

No abstract

Long-term follow-up confirms that patients with stage III NSCLC who receive 5 weeks of chemotherapy with cisplatin and vinblastine before radiation therapy have a 4.1-month increase in median survival. The use of sequential chemotherapy-radiotherapy increases the projected proportion of 5-year survivors by a factor of 2.8 compared with that of radiotherapy alone. However, inasmuch as 80%-85% of such patients still die within 5 years and because treatment failure occurs both in the irradiated field and at distant sites in patients receiving either sequential chemotherapy-radiotherapy or radiotherapy alone, the need for further improvements in both the local and systemic treatment of this disease persists.