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Addition of Etoricoxib During Concurrent Chemo-radiation of Cervical Cancer Patients Could Result in Faster Resolution of Gross Disease: A Prospective Single-Institution Study

  • Sovan Sarang DharEmail author
  • Uday Pratap Shahi
  • Deepak Kumar
  • Ritusha Mishra
  • Prashant Kaser
  • Satish Dewangan
  • Abhijit Mandal
  • Sunil Choudhary
  • Lalit Mohan Aggarwal
  • Anupam Kumar Asthana
  • Satyajit Pradhan
Original Article
  • 19 Downloads

Abstract

Objective

A prospective study was conducted to assess the effect of adding COX-2 inhibitor Etoricoxib during concurrent chemo-radiotherapy schedule of cervical cancer patients on tumour response and acute toxicities.

Materials and Methods

Forty patients of carcinoma cervix [mostly locally advanced] were treated using external beam radiotherapy (EBRT) [telecobalt, 45 Gy/20F/5F per week] concurrent with weekly cisplatin- or cisplatin + paclitaxel-based chemotherapy. Low-dose-rate (LDR) intracavitary brachytherapy (ICBT) 30 Gy to point A was delivered in between EBRT fractions in a single setting. Patients were prospectively allocated either to receive Etoricoxib 90 mg OD during the entire course of chemo-radiation [arm A] or not [arm B]. Weekly assessment with clinical evaluation and routine blood tests were done during the course of treatment, with pre-ICBT clinical evaluation taken into consideration for disease response comparison between arms.

Results

When evaluated clinically before intracavitary brachytherapy procedure, the gross disease was found to have regressed more in the arm receiving Etoricoxib [p = 0.042]. Acute grade-3 toxicities ranged between 5 and 15% for patients who received Etoricoxib and 10–15% for those who did not. Difference in toxicities was not statistically significant.

Conclusion

Addition of COX-2 inhibitor [Etoricoxib] during concurrent chemo-radiation results in a faster response of the primary disease in locally advanced cervical cancer patients, without a significant difference in acute toxicities.

Keywords

Locally advanced cervical cancer Concurrent chemo-radiation Etoricoxib Tumour response Acute toxicities 

Notes

Compliance with Ethical Standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):1–31.CrossRefGoogle Scholar
  2. 2.
    Dutta S, Biswas N, Muhkherjee G. Evaluation of socio-demographic factors for non-compliance to treatment in locally advanced cases of cancer cervix in a rural medical college hospital in India. Indian J Palliat Care. 2013;19(3):158–65.CrossRefGoogle Scholar
  3. 3.
    Doll CM, Winter K, Gaffney DK, et al. COX-2 expression and survival in patients with locally advanced treated with chemoradiotherapy and celecoxib: a quantitative immunohistochemical analysis of RTOG C0128. Int J Gynecol Cancer. 2013;23(1):176–83.CrossRefGoogle Scholar
  4. 4.
    Green JA, Kirwan JM, Tierney JF, et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001;358:781–6.CrossRefGoogle Scholar
  5. 5.
    Jung YW, Lee SH, Paek JH, et al. Acute toxicity of cyclooxygenase-2 inhibitor rofecoxib as a radiosensitizer for concurrent chemoradiation in the treatment of uterine cervical cancer. J Gynecol Oncol. 2009;20(3):151–7.CrossRefGoogle Scholar
  6. 6.
    Laube M, Kniess T, Pietzsch J. Development of antioxidant COX-2 inhibitors as radioprotective agents for radiation therapy—a hypothesis-driven review. Antioxidants (Basel). 2016;5(2):14.CrossRefGoogle Scholar
  7. 7.
    Saha D, Choy H. Potential for combined modality therapy of cyclooxygenase inhibitors and radiation. Prog Exp Tumor Res. 2003;37:193–209.CrossRefGoogle Scholar
  8. 8.
    Na YR, Yoon YN, Son DI, Seok SH. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model. PLoS ONE. 2013;8(5):e63451.CrossRefGoogle Scholar
  9. 9.
    Peng JP, Su CY, Chang HC, Chai CY, Hung WC. Overexpression of cyclo-oxygenase 2 in squamous cell carcinoma of the hypopharynx. Hum Pathol. 2002;33(1):100–4.CrossRefGoogle Scholar
  10. 10.
    Byatnal AA, Byatnal A, Sen S, Guddattu V, Solomon MC. Cyclooxygenase-2—an imperative prognostic biomarker in oral squamous cell carcinoma—an immunohistochemical study. Pathol Oncol Res. 2015;21(4):1123–31.CrossRefGoogle Scholar
  11. 11.
    Kuo KT, Chow KC, Wu YC, Lin CS, Wang HW, Li WY, Wang LS. Clinicopathologic significance of cyclooxygenase-2 overexpression in esophageal squamous cell carcinoma. Ann Thorac Surg. 2003;76(3):909–14.CrossRefGoogle Scholar
  12. 12.
    Jawanjal P, Salhan S, Dhawan I, Das N, Aggarwal R, Tripathi R, Rath G. Augmented activity of cyclooxygenase-2 in tissue and serum of patients with cervical cancer. J Clin Lab Anal. 2016;30(6):1198–207.CrossRefGoogle Scholar
  13. 13.
    Chen YJ, Wang LS, Wang PH, Lai CR, Yen MS, Ng HT, Yuan CC. High cyclooxygenase-2 expression in cervical adenocarcinomas. Gynecol Oncol. 2003;88(3):379–85.CrossRefGoogle Scholar
  14. 14.
    Munkarah A, Ali-Fehmi R. COX-2: a protein with an active role in gynecological cancers. Gynecol Oncol. 2008;109(1):140–5.CrossRefGoogle Scholar
  15. 15.
    Kim HJ, Wu HG, Park IA, Ha SW. High cyclooxygenase-2 expression is related with distant metastasis in cervical cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2003;55(1):16–20.CrossRefGoogle Scholar
  16. 16.
    Kim YB, Kim GE, Cho NH, Pyo HR, Shim SJ, Chang SK, Park HC, Suh CO, Park TK, Kim BS. Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy. Cancer. 2002;95(3):531–9.CrossRefGoogle Scholar
  17. 17.
    Chen HH, Su WC, Chou CY, Guo HR, Ho SY, Que J, Lee WY. Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63(4):1093–100.CrossRefGoogle Scholar
  18. 18.
    Choy H, Milas L. Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance? J Natl Cancer Inst. 2003;95(19):1440–52.CrossRefGoogle Scholar
  19. 19.
    Escudero-Condreas A, Cervantes JVM, Collantes-Estevez E. Update on the clinical Pharmacology of Etoricoxib, a potent cyclooxygenase-2 inhibitor. Future Rheumatol. 2007;2(6):545–65.CrossRefGoogle Scholar
  20. 20.
    Herrera FG, Chan P, Doll C, Milosevic M, Oza A, Syed A, Pintilie M, Levin W, Manchul L, Fyles A. A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment. Int J Radiat Oncol Biol Phys. 2007;67(1):97–103.CrossRefGoogle Scholar
  21. 21.
    Kirwan JM, Symonds P, Green JA, Tierney J, Collingwood M, Williams CJ. A systematic review of acute and late toxicity of concomitant chemo-radiation for cervical cancer. Radiother Oncol. 2003;68:217–26.CrossRefGoogle Scholar
  22. 22.
    Jeyaseelan V, Pavamani SP, Ram TS, Thomas EM, Varghese SS, Viswanathan PN. Concurrent chemo-irradiation with weekly cisplatin and paclitaxel in the treatment of locally advanced squamous cell carcinoma of cervix: a phase II study. J Cancer Res Ther. 2014;10(2):330–6.CrossRefGoogle Scholar
  23. 23.
    Saibishkumar EP, Patel FD, Sharma SC. Results of a phase II trial of concurrent chemo-radiation in the treatment of locally advanced carcinoma of uterine cervix: an experience from India. Bull Cancer. 2005;92(1):E7–12.PubMedGoogle Scholar

Copyright information

© Association of Gynecologic Oncologists of India 2019

Authors and Affiliations

  • Sovan Sarang Dhar
    • 1
    • 2
    Email author
  • Uday Pratap Shahi
    • 1
  • Deepak Kumar
    • 1
    • 3
  • Ritusha Mishra
    • 1
  • Prashant Kaser
    • 1
    • 4
  • Satish Dewangan
    • 1
  • Abhijit Mandal
    • 1
  • Sunil Choudhary
    • 1
  • Lalit Mohan Aggarwal
    • 1
  • Anupam Kumar Asthana
    • 1
  • Satyajit Pradhan
    • 1
  1. 1.Department of Radiotherapy and Radiation Medicine, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia
  2. 2.Department of RadiotherapyAll India Institute of Medical Sciences, BhubaneswarBhubaneswarIndia
  3. 3.Department of RadiotherapyAll India Institute of Medical Sciences, New DelhiNew DelhiIndia
  4. 4.Department of RadiotherapyPt. Jawaharlal Nehru Memorial Medical CollegeRaipurIndia

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