Abstract
Background
This randomized clinical study was conducted to evaluate the therapeutic benefits
of cytokine-induced killer (CIK) cell immunotherapy in combination with chemotherapy
in metastatic colorectal cancer (mCRC) patients.
Patients and Methods
Sixty-one patients in group 1 (cell therapy group) received autologous CIK cell immunotherapy
in combination with chemotherapy (5-Fluorouridine, leucovorin and oxaliplatin [FOLFOX4]
plan). Another 61 patients in group 2 (the control group) received chemotherapy (FOLFOX4
plan) alone. The primary study end points were overall survival (OS) and progression-free
survival (PFS). The secondary end points were treatment response and adverse events.
Results
The 3-year PFS and OS in group 1 were 20% and 48%, respectively, compared with 13%
and 23%, respectively, in group 2 (P = .131 and P < .001, respectively). The median OS in group 1 was significantly increased compared
with that in group 2 (OS, 36 vs. 16 months; P < .001). Furthermore, there was a trend toward superior PFS in group 1 compared with
that in group 2 (PFS, 16 vs. 10 months; P = .072). Using univariate analysis, we found that Karnofsky performance status <80,
number of metastases >1, and increased platelet levels were significantly associated
with poorer prognosis in group 1. Alternatively, the cycle count of CIK cell treatment
was significantly associated with good prognosis in group 1. Toxicity was mild in
patients who received CIK therapy.
Conclusion
This study shows that CIK cell immunotherapy in combination with chemotherapy is well
tolerated and improves the OS of mCRC patients.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Colorectal CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global cancer statistics.CA Cancer J Clin. 2011; 61: 69-90
- Towards a pan-European consensus on the treatment of patients with colorectal liver metastases.Eur J Cancer. 2006; 42: 2212-2221
- Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study.J Clin Oncol. 2007; 25: 4779-4786
- FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.J Clin Oncol. 2004; 22: 229-237
- A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.J Clin Oncol. 2004; 22: 23-30
- Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.N Engl J Med. 2004; 350: 2335-2342
- Annual report to the nation on the status of cancer, 1975-2001, with a special feature regarding survival.Cancer. 2004; 101: 3-27
- Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis.J Clin Oncol. 2004; 22: 3766-3775
- Immune therapy for cancer.Annu Rev Immunol. 2009; 27: 83-117
- Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC).J Cancer Res Clin Oncol. 2011; 137: 305-310
- Developments in clinical cell therapy.Cytotherapy. 2010; 12: 425-428
- Lymphokine-activated killer cells: a new approach to immunotherapy of cancer.J Natl Cancer Inst. 1985; 75: 595-603
- In vivo antitumor activity of anti-CD3-induced activated killer cells.Cancer Res. 1989; 49: 4770-4774
- Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity.J Exp Med. 1991; 174: 139-149
- Th1 bias in PBMC induced by multicycles of auto-CIKs infusion in malignant solid tumor patients.Cancer Biother Radiopharm. 2006; 21: 22-33
- Autologous cytokine-induced killer cell immunotherapy in lung cancer: a phase II clinical study.Cancer Immunol Immunother. 2012; 61: 2125-2133
- Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma.Clin Cancer Res. 2012; 18: 1751-1759
- Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma.Br J Cancer. 1999; 81: 1009-1016
- Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale.J Clin Oncol. 2005; 23: 4866-4875
- Response evaluation criteria in solid tumors (RECIST): new guidelines.Med Pediatr Oncol. 2001; 37: 1-3
- A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer.Cancer. 1992; 69: 893-900
- 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. 2009; 11: 1076-1083
- Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer.J Clin Oncol. 2009; 27: 663-671
- Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study.J Clin Oncol. 2010; 28: 4697-4705
- First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer.J Cancer Res Clin Oncol. 2012; 138: 65-72
- Clinical and cost effectiveness of bevacizumab + FOLFIRI combination versus FOLFIRI alone as first-line treatment of metastatic colorectal cancer in South Korea.Clin Ther. 2012; 34: 1408-1419
- Multicenter, randomized phase II trial of bevacizumab plus folinic acid, fluorouracil, gemcitabine (FFG) versus bevacizumab plus folinic acid, fluorouracil, oxaliplatin (FOLFOX4) as first-line therapy for patients with advanced colorectal cancer.Invest New Drugs. 2012; 30: 772-778
- Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice.Future Oncol. 2012; 8: 1193-1197
- Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer.Oncology. 2009; 77: 113-119
- Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study.J Clin Oncol. 2010; 28: 3191-3198
- Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status.J Clin Oncol. 2011; 29: 2011-2019
- Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients.J Clin Oncol. 2005; 23: 8950-8958
Article info
Publication history
Published online: February 15, 2016
Accepted:
February 3,
2016
Received in revised form:
December 31,
2015
Received:
November 16,
2015
Footnotes
Hua Zhao and Yang Wang contributed equally to this report.
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
