Case Report: CEA Elevation Can Be a Marker of Increased Inflammation During Treatment with Oxaliplatin (2024)

Abstract

Oxaliplatin is a platinum-based chemotherapy that is an integral part of several regimens for colorectal cancer. We present the case of a patient, a 58-year-old male, who had initially presented aged 56 years with rectal bleeding for several months. His serum carcinoembryonic antigen (CEA) level at the time of diagnosis was 4.6 ng/ml. His CEA level increased significantly during oxaliplatin-based chemotherapy and declined to a near normal level after completion of therapy. There was no evidence of disease during this time and he remains disease-free. Oxaliplatin has been shown to cause an inflammatory response which appears to be one of the mechanisms of toxicity and high CEA levels have been correlated with increased inflammation. We postulate that this patient's rising CEA level was secondary to an inflammatory response to oxaliplatin-based therapy, which is further supported by the subsequent decrease after completion of chemotherapy. To our knowledge, this is the first published case of oxaliplatin-induced rising CEA level.

Case Report

The patient was a 58-year-old male who had initially presented aged 56 years with rectal bleeding for several months. Colonoscopy was performed revealing invasive adenocarcinoma 25 cm from the anal verge. His serum CEA level at the time of diagnosis was 4.6 ng/ml. Imaging did not reveal any metastatic lesions. The patient underwent robotic-assisted laparascopic rectosigmoidal resection with intraoperative liver ultrasound. Final pathology revealed poorly differentiated adenocarcinoma, 4.2 cm in greatest dimension, invading into the subserosal adipose tissue (pT3) with lymphovascular invasion. There were 3/33 cancer-positive lymph nodes. The final tumor stage was pT3N1bM0, stage 3B. Surgical margins were negative and there were no complications. The patient was then referred to Medical Oncology to initiate adjuvant chemotherapy and was started on FOLFOX (oxaliplatin at 85 mg/m²) 6 weeks after resection. The patient's CEA level at the beginning of chemotherapy was 4.7 ng/ml, which increased to 7.7 ng/ml after three cycles (Figure 1). Treatment was held in order to determine possible disease recurrence. Computed tomographic (CT) scans were negative as was a follow-up positron-emission tomography (PET). The patient underwent colonoscopy which showed postoperative changes with no evidence of malignancy. Chemotherapy was resumed and he completed 12 cycles of FOLFOX. As shown in Figure 1, his serum CEA level continued to rise, peaking at 18.3 ng/ml during his last chemotherapy cycle. Follow-up imaging, which included PET/CT and magnetic resonance imaging of the abdomen, remained negative as was subsequent colonoscopy. After completing chemotherapy, the serum CEA level began to decline to 5.1 ng/ml. At 21 months post-resection the patient remains disease-free.

Discussion

Herein, we present a patient with colon adenocarcinoma who initially had a normal CEA level at diagnosis. His CEA increased significantly during oxaliplatin-based chemotherapy and this declined to near normal level after completion of therapy. There was no evidence of disease during this time and he remains disease-free.

For patients with colonic adenocarcinoma receiving adjuvant chemotherapy, any rise in CEA level should prompt thorough evaluation for disease recurrence; however, in the absence of disease, it should be noted that inflammatory changes could be the trigger of a CEA rise. This should especially be noted in patients who present with a normal or mildly elevated CEA level at diagnosis. While other inflammatory markers (e.g. C-reactive protein) were not evaluated in this patient, these may be considered in patients with a rising CEA level not explained by malignancy.

A number of studies have shown a correlation of CEA level and various inflammatory states. For example, an increased CEA level was correlated with lung disease in patients with rheumatoid arthritis (15). A study of patients with allergic bronchopulmonary aspergillosis showed anelevated CEA level that decreased after treatment (16). Furthermore, in a recent study on a large population of Korean adults (n=19,834), CEA was positively correlated with white blood cell count (17).

Oxaliplatin has been shown to cause an inflammatory response, which appears to be one of its mechanisms of toxicity, and a raised CEA level has been correlated with increased inflammation (17). Given the known inflammatory changes that can occur with oxaliplatin therapy and that the CEA level is also increased in other inflammatory conditions, we postulate that this patient's rising CEA level was secondary to an inflammatory response to oxaliplatin-based therapy, which is further supported by the subsequent decrease in CEA after completion of chemotherapy.

To our knowledge, this is the first published case of oxaliplatin-induced rising CEA level.

Footnotes

• Conflicts of Interest

  The Authors received no funding for this work and have no conflicts of interest related to this work or financial relationships to report in regard to this study.

References

1. ↵
   1. Zwelling LA,
   2. Anderson T,
   3. Kohn KW

   : DNA-protein and DNA interstrand cross-linking by cis- and trans-platinum(II) diamminedichloride in L1210 mouse leukemia cells and relation to cytotoxicity. Cancer Res 39(2 Pt 1): 365-369, 1979.

   OpenUrlAbstract/FREE Full Text

2. ↵
   1. Ramanathan RK,
   2. Clark JW,
   3. Kemeny NE,
   4. Lenz HJ,
   5. Gococo KO,
   6. Haller DG,
   7. Mitchell EP,
   8. Kardinal CG

   : Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer. J Clin Oncol 21(15): 2904-2911, 2003.

   OpenUrlAbstract/FREE Full Text

3. ↵
   1. Argyriou AA,
   2. Polychronopoulos P,
   3. Iconomou G,
   4. Chroni E,
   5. Kalofonos HP

   : A review on oxaliplatin-induced peripheral nerve damage. Cancer Treat Rev 34(4): 368-377, 2008.

   OpenUrlCrossRefPubMed

   See Also

   CEA Test (Carcinoembryonic Antigen): What It Is & Results
4. ↵
   1. Joseph EK,
   2. Chen X,
   3. Bogen O,
   4. Levine JD

   : Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy. J Pain 9(5): 463-472, 2008.

   OpenUrlCrossRefPubMed

5. ↵
   1. Wang YS,
   2. Li YY,
   3. Cui W,
   4. Li LB,
   5. Zhang ZC,
   6. Tian BP,
   7. Zhang GS

   : Melatonin attenuates pain hypersensitivity and decreases astrocyte-mediated spinal neuroinflammation in a rat model of oxaliplatin-induced pain. Inflammation 40(6): 2052-2061, 2017.

   OpenUrl

6. ↵
   1. Makker PG,
   2. Duffy SS,
   3. Lees JG,
   4. Perera CJ,
   5. Tonkin RS,
   6. Butovsky O,
   7. Park SB,
   8. Goldstein D,
   9. Moalem-Taylor G

   : Characterisation of immune and neuroinflammatory changes associated with chemotherapy-induced peripheral neuropathy. PLoS One 12(1): e0170814, 2017.

   OpenUrl

7. ↵
   1. Moskovitz M,
   2. Wollner M,
   3. Haim N

   : Oxaliplatin-induced pulmonary toxicity in gastrointestinal malignancies: two case reports and review of the literature. Case Rep Oncol Med 2015: 341064, 2015.

   OpenUrl

8. ↵
   1. Wilcox BE,
   2. Ryu JH,
   3. Kalra S

   : Exacerbation of pre-existing interstitial lung disease after oxaliplatin therapy: a report of three cases. Respir Med 102(2): 273-279, 2008.

   OpenUrlCrossRefPubMed

9. ↵
   1. Bae U,
   2. Shim JY,
   3. Lee HR,
   4. Shin JY

   : Serum carcinoembryonic antigen level is associated with arterial stiffness in healthy Korean adult. Clin Chim Acta 415: 286-289, 2013.

   OpenUrl

10. 1. Bulut I,
    2. Arbak P,
    3. Coskun A,
    4. Balbay O,
    5. Annakkaya AN,
    6. Yavuz O,
    7. Gulcan E

    : Comparison of serum CA 19.9, CA 125 and CEA levels with severity of chronic obstructive pulmonary disease. Med Princ Pract 18(4): 289-293, 2009.

    OpenUrlPubMed

11. 1. Lee JW,
    2. Park KD,
    3. Im JA,
    4. Hwang HJ,
    5. Kim SH

    : Serum carcinoembryonic antigen is associated with metabolic syndrome in female Korean non-smokers. Clin Chim Acta 412(7-8): 527-530, 2011.

    OpenUrlPubMed

12. ↵
    1. Park JS,
    2. Choi GS,
    3. Jang YS,
    4. Jun SH,
    5. Kang H

    : Influence of obesity on the serum carcinoembryonic antigen value in patients with colorectal cancer. Cancer Epidemiol Biomarkers Prev 19(10): 2461-2468, 2010.

    OpenUrlAbstract/FREE Full Text

13. ↵
    1. Aarons CB,
    2. Bajenova O,
    3. Andrews C,
    4. Heydrick S,
    5. Bushell KN,
    6. Reed KL,
    7. Thomas P,
    8. Becker JM,
    9. Stucchi AF

    : Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells. Clin Exp Metastasis 24(3): 201-209, 2007.

    OpenUrlCrossRefPubMed

14. ↵
    1. Ganguly A,
    2. Yeltsin E,
    3. Robbins J

    : Identification of a carcinoembryonic antigen binding protein on monocytes. Biochem Biophys Res Commun 311(2): 319-323, 2003.

    OpenUrlCrossRefPubMed

15. ↵
    1. Koch MC,
    2. Pereira IA,
    3. Nobre LF,
    4. Neves FS

    : Computed tomography of pulmonary changes in rheumatoid arthritis: carcinoembryonic antigen (CEA) as a marker of airway disease. Rheumatol Int 36(4): 531-539, 2016.

    OpenUrl

16. ↵
    1. Noguchi T,
    2. Yamamoto K,
    3. Moriyama G,
    4. Saito Y,
    5. Kyoyama H,
    6. Mikami S,
    7. Ono R,
    8. Kobayashi T,
    9. Yamana K,
    10. Uematsu K

    : Evaluation of serum levels of carcinoembryonic antigen in allergic bronchopulmonary aspergillosis. J Nippon Med Sch 80(6): 404-409, 2013.

    OpenUrl

17. ↵
    1. Kwon YJ,
    2. Lee HS,
    3. Shim JY,
    4. Lee YJ

    : Serum carcinoembryonic antigen is positively associated with leukocyte count in Korean adults. J Clin Lab Anal, 2017. doi: 10.1002/jcla.22291. [Epub ahead of print]