A phase III randomized study of interleukin-2 lymphokine-activated killer cell immunotherapy combined with chemotherapy or radiotherapy after curative or noncurative resection of primary lung carcinoma.

Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has resulted in response among some patients with advanced malignant disease. However, the relative therapeutic benefit of adoptive immunotherapy as an adjuvant to surgery has not been determined. A Phase III prospective randomized controlled study of adjuvant immunotherapy combined with chemotherapy or radiotherapy was conducted for 174 primary lung carcinoma patients postsurgically. After a pathologic examination of resected tissues, patients were divided into curative and noncurative cases and randomized to receive either combined immunotherapy (Group A) or control standard therapy (Group B). Patients who had undergone curative resection of lung carcinoma were stratified according to the stages and histologic types of their disease, and those who had undergone noncurative resection were stratified according to the causes of noncurative resection. The patients of Group A received IL-2 and LAK cells after either chemotherapy or radiotherapy, and those in Group B received either no adjuvant therapy (curative cases) or radiotherapy or chemotherapy alone (noncurative cases), according to the causes of noncurative resection. The 5- and 9-year survival rates of the Group A patients were 54.4% and 52.0%, respectively, and those of the Group B patients were 33.4% and 24.2%, respectively. The difference was statistically significant (P < 0.001, according to the generalized Wilcoxon's test and the Cox-Mantel test). The difference was also statistically significant in the curative cases (65.5% for Group A vs. 40.6% for Group B; 5-year survival rate, P < 0.01), noncurative cases (43.0% for A vs. 20.8% for B; P < 0.01), adenocarcinoma cases (47.5% for A vs. 23.0% for B; P < 0.05), and squamous cell carcinoma cases (62.1% for A vs. 34.8% for B; P < 0.01). Adoptive immunotherapy with IL-2 and LAK cells combined with chemotherapy or radiotherapy improved the survival of patients after surgical resection of primary lung carcinoma. A multi-institutional group study should be carried out to verify the significance of this study.