About Onko-Sure®

When you know, you can act.

Onko-Sure® is a simple, non-invasive and FDA cleared in vitro diagnostic (IVD) blood biomarker test used both for monitoring colorectal cancer (CRC) during treatment and afterwards for recurrence monitoring. It helps CRC patients and their healthcare team of physicians plan a pro-active treatment program and follow-up plan for patients after a CRC diagnosis.

In medical terms, it measures Fibrin/Fibrinogen Degradation Products (FDP) in the blood serum. If these elements are found to be present, the physician can use this information to better plan and focus the post-diagnosis treatment program. Identifying colorectal cancer recurrences earlier and treating it properly can lead to a better survival rate and quality of life.1

Note: Onko-Sure® is available in the United States for monitoring of CRC treatment and recurrence.

Onko-Sure® offers some specific advantages over other approaches:

  • Simple, non-invasive blood test
  • Clinically proven in 12 published studies for monitoring of colorectal cancer treatment and recurrence
  • Floats freely in blood (which makes it more effective even in lower concentrations of the marker)

Here are some of the details—and don’t worry if this is a bit over your head. Your physician can help explain:

For the last 25 years, Carcinoembryonic Antigen (CEA) (sensitivity of 38-69%) and CA 19-9 (sensitivity of 23-65%) have been available blood biomarkers for colorectal cancer (CRC) treatment and follow-up monitoring. However, similar to any other biomarker, they have their own limitations.1 DR-70® (sensitivity of 54-87%) is the most recent biomarker cleared by the US FDA for the monitoring of colorectal cancer treatment and recurrence. It has been shown by two recent clinical studies performed in the UK and US in 2010 that combining CEA and DR-70® improves the test sensitivity to 55% higher than that of CEA alone.

How Onko-Sure® Works

The production of Fibrin and Fibrinogen Degradation Products (FDP) is restricted in healthy individuals by normal cells. However, cancer cells release proteolytic enzymes such as plasmin and thrombin as they grow and metastasize. They also redirect the coagulation cascade which leads to overproduction of FDP in the process of carcinogenesis.2-4

FDP level measurement is routinely performed for the detection of coagolopathies. However, the current assays for FDP measurement usually detect only one out of the many FDP components (D-dimer).5 There have been many publications studying the D-dimer level measurement in different malignancies including CRC6-9; however, it is not approved for detecting or monitoring malignancies.

Onko-Sure® is the first blood test available for the monitoring of colorectal cancer treatment and recurrence based on FDP measurement. It is an ELISA-based test that uses DR-70® polyclonal antibody against the full array of FDP. Onko-Sure® detects all of the breakdown products of Fibrin and Fibrinogen, including a unique cancer-related breakdown product, Initial Plasmin Degradation Product (IPDP).10

Clinical data supports the medical utilization of Onko-Sure® for the monitoring of colorectal cancer. In these seven clinical studies, Onko-Sure® was used to measure DR-70 levels in about 6,000 patients and the results positively correlated with the progression of CRC.1,10-14 Furthermore, as reported by six other studies, the D-dimer level was also linked to CRC progression in about 500 patients.2,6-9

Comparison of Onko-Sure® with CEA

CEA, an adhesion molecule, is firmly attached to cancer cells.15 Therefore, it is less abundant in blood and more difficult to be measured. However, DR-70 antigen is freely diffusible in blood and therefore easy to measure even in low concentrations in lower stages of the cancer. Approximately 35% of all CRC patients experience recurrence.16 Of those, half of them have low CEA values not detectable by CEA test.17-19  For this reason, Onko-Sure® has advantages over CEA in detecting lower levels of this biomarker leading to an early detection of recurrence.

Figure 1. Comparison of Onko-Sure® with CEA. A large number of CRC patients have low CEA values (Concordance with Clinical Findings (%)

The Concentration of Biomarker (ng/ml)

(CEA = Carcinoembryonic Antigen)

CEA has approximately a 20% chance of false positive in smokers20 while Onko-Sure® measurements are not affected by smoking.

In general, it has been found that a combination of several biomarkers provides more accurate information for CRC monitoring. Therefore, it is recommended that both CEA and Onko-Sure® are used in combination for the monitoring of post-surgery CRC recurrence21.

More clinical studies are ongoing to verify the beneficial effect of CEA combination with Onko-Sure®. Furthermore, Onko-Sure® should be used in conjunction with other clinical modalities considered to be the standard of care for CRC disease progression monitoring.

Summary

Onko-Sure® is a simple, non-invasive, patent-pending blood test used both for monitoring colorectal cancer (CRC) during treatment and for post-treatment CRC recurrence. It is an ELISA-based assay that measures the accumulation of Fibrin/Fibrinogen Degradation Products (FDP) in the serum using a polyclonal antibody (DR-70) as a blood biomarker.

For the last 25 years, CEA has been the main routine biomarker for CRC monitoring. DR-70 is the most recent biomarker cleared by the US FDA for the monitoring of colorectal cancer treatment and recurrence. It is recommended to use these two tests in combination to increase the test sensitivity for the monitoring of CRC treatment and recurrence (supported by 2 clinical studies in 2011).

The information on this website is intended for healthcare professionals practicing in the US. If you or a loved one want to know more about Onko-Sure, we encourage you to discuss it with your physician or other healthcare professional.

References

1. Anthony T. Colorectal cancer follow-up in 2005. Surg Oncol Clin N Am. 2006;15:175-193.

2. Okholm M, Iversen, LH, Thorlacius-Ussing O, Ejlerson E, Boesby S. Fibrin and fibrinogen degredation products in plasma of patients with colorectal adenocarcinoma. Dis Colon Rectum. 1996;39:1102-1106.

3. Hatton MW. Fibrinogen catabolism within the procoagulant VX-2 tumor of rabbit lung in vivo: Effluxing fibrin(ogen) fragments contain antiangiogenic activity. J Lab Clin Med. 2004;143:241-254.

4. Hatton MW. Relationships among tumor burden, tumor size, and the changing concentrations of fibrin degredation products and fibrinolytic factors in the pleural effusions of rabbits with VX2 lung tumors. J Lab Clin Med. 2006; 147:27-35.

5. Ieko M, Nakabayashi T, Tarumi T, Naito S, Yoshida M, Kanazawa K, Mizukami K, Koike T. Soluble fibrin monomer degradation products as a potentially useful marker for hypercoagulable states with accelerated fibrinolysis. Clin Chim Acta. 2007;386(1-2):38-45.

6. Blackwell K, Hurw´itz H, Liebe´rman G, Novotny W, Snyder S, Dewhirst M, Greenberg C. Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma. cancer. 2004;101(1):77-82.

7. Kilic M, Yoldas O, Keskek M, Ertan T, Tez M, Gocmen E, Koc M. Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Colorectal Dis. 2008;10(3):238-41.

8. Oya M, Akiyama Y, Yanagida T, Akao S, Ishikawa H. Plasma D-dimer level in patients with colorectal cancer: its role as a tumor marker. Surg Today. 1998;28(4):373-8.

9. Xu G, Ya-Li Zhang, Wen Huang. Relationship between plasma D-dimer levels and clinicopathologicparameters in resectable colorectal cancer patients. World J Gastroenterol. 2004;10(6):922-923.

10. Rucker P, Antonio SM and Braden B. Elevated Fibrinogen-Fibrin Degradation Products (FDP) in Serum of Colorectal Cancer Patients. Analytical Letters. 2004;37:2965-2976.

11. Kerber A, TrojanJ, Herrlinger K, Zgouras D, Caspary WF, Braden B. The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study. Aliment Pharmacol Ther. 2004;20:983-098.

12. Small-Howard A, Harris H. Advantages of the AMDL-ELISA DR-70 (FDP) Assay over Carcinoembryonic Antigen for Monitoring Colorectal Cancer Patients. J Immunoassay Immunochem. 2010;31(2):131-147.

13. Wu D, Zhou X, Yang G, et al. Clinical performance of the AMDL DR-70 immunoassay kit for cancer detection. J Immunoassay 1998;19(1):63-72.

14. Lee KH, Cho DH, Kim KM, et al. Meaning of the DR-70 immunoassay for patients with the malignant tumor. Immune Network 2006;6(1):43-51.

15. Charalabopoulos K. CEA levels in serum and BAL in patients suffering from lung cancer: correlation with individuals presenting benign lung lesions and healthy volunteers. Med Oncol. 2007;24:219-225.

16. Graffner H, Hultberg B, Johansson B, Moller T, Petersson BG. Detection of recurrent cancer of the colon and rectum. J Surg Oncol. 1985;28:156-159.

17. Ladenson JH, McDonald JM, Landt M, Schwartz MK. Colorectal carcinoma and carcinoembryonic antigen (CEA). Clin Chem. 1980;26:1213-1220.

18. Wang JY, Tang R, Chiang JM. Value of carcinoembryonic antigen in the management of colorectal cancer. Dis Colon Rectum. 1994;37:272-277.

19. Wang WS. Preoperative carcinoembryonic antigen level as independent prognostic factor in colorectal cancer. Taiwan experience. Jpn J Clin Oncolo. 2000;30:12-16.

20. Kantrowitz M. False Positives and False Negativesin Tumor Marker Blood Tests. Cancer Points.http://www.kantrowitz.com/cancerpoints/tumormarkerfalsepositives.html[01/06/2010 11:59:54 PM].

21. Shimwell NJ, Wei W, Wilson S, et al. Assessment of novel combinations of biomarkers for the detection of colorectal cancer. Cancer Biomark. 2010;7(3):123-132.