Abstract
Background
Lung cancer is the leading cause for cancer-related mortality and morbidity, and the survival of late-stage non-small cell lung cancer (NSCLC) remains poor. We hereby evaluate conventional chemotherapy followed by immunotherapy using dendritic cells and cytokine-induced killer cells in the treatment for late stage of NSCLC.
Methods
Twenty-eight untreated patients suffered from IIIB to IV NSCLC were enrolled in the study between August 2004 and October 2005, and all received four courses of vinorelbine–platinum (NP) chemotherapy. Fourteen of them received conventional NP chemotherapy followed by vaccinated with CEA (605–613) peptide-pulsed autologous dendritic cells and CIK cells. Vaccination was repeated at 30-day intervals for 4 cycles. The adverse effects, time to progression (TTP), and overall survival (OS) in each group were evaluated.
Results
The adverse effect as a result of chemoimmunotherapy was mild and tolerable. Rash, acne, and pruritus were more frequent in the chemoimmunotherapy group than in the chemotherapy group (64.2% vs. 7.1%, P = 0.004). Non-infectious fever was more frequent in the chemoimmunotherapy group than in the chemotherapy group (71.4% vs. 21.4% P = 0.02). Less grade 3/4 fatigue was observed in patients receiving chemoimmunotherapy: 7.1% versus 57.1% in chemotherapy group, P = 0.01. Compared with patients in chemotherapy group, time to progression in chemoimmunotherapy significantly prolonged, with the median improved from 5.2 months (95% CI: 3.3–6.0) to 6.9 months (95% CI: 5.0–8.8) (P = 0.03). The 1-, 2-, and 5-year survival rates were 64.3, 49, and 21.0%, respectively in chemoimmunotherapy group. Overall survival rate showed no statistically difference between two groups (P = 0.18).
Conclusions
Chemoimmunotherapy could alleviate adverse effects of conventional chemotherapy and prolong survival for patients with late-stage NSCLC.
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References
Jemal A, Tivare RC, Murray T, Ghafoor A, Samuels A, Ward E et al (2004) Cancer statistics. CA Cancer J Clin 54:8–29
Sun JM, Park JO, Won YW, Kim JH, Yun J, Lee J, Park YH, Ahn JS, Ahn MJ, Park K (2010) Who are less likely to receive subsequent chemotherapy beyond first-line therapy for advanced non-small cell lung cancer? Implications for selection of patients for maintenance therapy. J Thorac Oncol 5(4):540–545
Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98
Kelly RJ, Gulley JL, Giaccone G (2010) Targeting the immune system in non-small-cell lung cancer: bridging the gap between promising concept and therapeutic reality. Clin Lung Cancer 11(4):228–237 Review
Gérard C, Debruyne C (2009) Immunotherapy in the landscape of new targeted treatments for non-small cell lung cancer. Mol Oncol 3(5–6):409–424 [Epub 10 Sep 2009. (Review)]
Cranmer LD, Trevor KT, Hersh EM (2004) Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother 53:275–306
Mocellin S, Mandruzzato S, Bronte V, Lise M, Nitti D (2004) Part I. Vaccines for solid tumours. Lancet Oncol 5:681–689
Nestle FO, Farkas A, Conrad C (2005) Dendritic-cell-based therapeutic vaccination against cancer. Curr Opin Immunol 17:163–169
Ming S, Bing Z, Zi-Rong T et al (2004) Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma. World J Gastroenterol 10(8):1146–1151
Hui L, Changli W, Jinpu Y et al (2009) Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery. Cytotherapy 11(8):1076–1083
Susan EA, Jose RG, Martin S et al (1998) Dendritic cells pulsed with CEA peptide induced CEA-specific CTL with restricted TCR repertoire. J Immunother 21(1):17–26
Marten A, Ziske C, Schottker B et al (2001) Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations. J Immunother 24(6):502–510
Kaneno R, Shurin GV, Tourkova IL, Shurin MR (2009) Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations. J Transl Med 7:58
Shurin GV, Tourkova IL, Kaneno R, Shurin MR (2009) Chemotherapeutic agents in noncytotoxic concentrations increase antigen presentation by dendritic cells via an IL-12-dependent mechanism. J Immunol 183(1):137–144 E pub 2009 Jun 17
Zhong H, Han B, Tourkova IL, Lokshin A, Rosenbloom A, Shurin MR, Shurin GV (2007) Low-dose paclitaxel prior to intratumoral dendritic cell vaccine modulates intratumoral cytokine network and lung cancer growth. Clin Cancer Res 13(18 Pt 1):5455–5462
Acknowledgments
This research was supported by Nature Science Foundation of Shanghai, China (No.: 10ZR1428200).
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Runbo Zhong and Jiajun Teng contributed equally to this work.
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Zhong, R., Teng, J., Han, B. et al. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immunother 60, 1497–1502 (2011). https://doi.org/10.1007/s00262-011-1060-0
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DOI: https://doi.org/10.1007/s00262-011-1060-0