Randomized controlled phase III trial of adjuvant chemo-immunotherapy with activated killer T cells and dendritic cells in patients with resected primary lung cancer

Abstract

PurposeWe conducted a phase III randomized controlled trial (RCT) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy. The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy.Patients and methodsBetween April 2007 and July 2012, 103 postsurgical non-small cell lung cancer patients were randomly assigned to receive either chemo-immunotherapy (group A) or chemotherapy (group B). The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients’ own regional lymph nodes.ResultsThe 2-year overall survival rates in groups A and B were 93.4 and 66.0 %, and the 5-year rates were 81.4 and 48.3 %, respectively. The differences were statistically significantly better in group A. The hazard ratio (HR) was 0.229 (p = 0.0013). The 2- and 5-year recurrence-free survival rates were 68.5, 41.4 and 56.8, 26.2 % in groups A and B, respectively. Those differences were also statistically significant (log-rank test p = 0.0020). The HR was 0.423 (p = 0.0027) in favor of group A. As for adverse reactions to immunotherapy, of a total of 762 courses, 52 (6.8 %) were accompanied with chills and shivering, and 47 (6.2 %), with fever (>38 °C).ConclusionsImmunotherapy has the potential to improve the postsurgical prognosis of lung cancer patients, but a large-scale multi-institutional RCT is awaited for further confirmation of this study.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-014-1613-0) contains supplementary material, which is available to authorized users.

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

“…Thus far, no clinical trials have been reported that exclusively tested the combination of chemotherapy and DC vaccination, but numerous trials are ongoing in which the combination is being tested with or without additional therapies. Chemotherapy and DC vaccination were tested with the addition of a COX-2 inhibitor in melanoma in a phase III trial showing encouraging data, and with the addition of autologous T cells in lung cancer in two randomized trials showing longer overall survival compared with outcomes from chemotherapy alone (79)(80)(81).…”

A case of testicular germ cell carcinoma identified five years after lung metastasis resection

“…No distant metastases were confirmed by routine examinations for lung cancer using computed t node disse adenocarci chemothera to Novemb dendritic ce The total c number of and lymph mary lung d adjuvant ) from July onths with rgery [6][7][8][9][10] .…”

Dendritic Cells in Human Lung Disease

“…There is much interest in utilizing DC-based vaccines in combination with activated killer T-cells to enhance the host anti-tumor response in lung cancer. Though some early studies have shown promising results in patients with surgically resected non-small cell lung cancer 55 , confirmation in large multi centre studies are needed.…”