Skip to main content

Nimotuzumab with Concurrent Chemoradiation in the Treatment of Locally Advanced Cervical Cancer: A Single-Centre Experience

Indian Journal of Gynecologic Oncology volume 18, Article number: 92 (2020) Cite this article

Abstract

Purpose

Outcomes with chemoradiation (CTRT) in the treatment of locally advanced cervical cancer (LACC) have plateaued. Combining an anti-epidermal growth factor receptor (EGFR) to CTRT could confer added advantage. Hence, we evaluated safety and efficacy of an anti-EGFR humanized monoclonal antibody-nimotuzumab, when given concurrent with CTRT in the treatment of LACC.

Methods

We retrospectively collected and analysed patients with LACC treated with nimotuzumab with concurrent CTRT from 2013 to 2016 at a single centre in Jabalpur, Madhya Pradesh.

Results

A total of 13 patients were evaluated. With a median follow-up of 47 months (range 35–77), 100% patients were alive till last follow-up date. All (100%) patients achieved complete response. The 2-, 3-, 4- and 5-year follow-up data were available for 100%, 92.3%, 46.1% and 30.7% patients, respectively. The disease-free survival and overall survival rate at 2 years were 100% and 100%, at 3 years 100% and 100%, at 4 years 83.3% and 100% and at 5 years 75% and 100%, respectively. Most commonly observed adverse events were grade 1 loose motion (61.53%) and vomiting (53.84%). Grade 2 vomiting was observed in 7.67% patients. No grade 3 and 4 adverse events were observed.

Conclusion

Nimotuzumab when given with concurrent CTRT in the treatment of LACC-improved disease-free survival, overall survival and tumour response without additional toxicity. Further studies are required in large number of patients to validate these findings.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. International Agency for Research on Cancer, World Health Organization. Global Cancer Observatory. https://gco.iarc.fr/. Accessed 03 Jan 2020.

  2. India State-Level Disease Burden Initiative Cancer Collaborators. The burden of cancers and their variations across the states of India: the Global Burden of Disease Study 1990–2016. Lancet Oncol. 2018;19(10):1289–306.

    Article  Google Scholar 

  3. Kumari A, Pankaj S, Choudhary V, Kumari A, Nazneen S, Kumari J, et al. Retrospective analysis of patients of cervical cancer a tertiary center in Bihar. Indian J Cancer. 2018;55(1):70–3.

    Article  Google Scholar 

  4. Sharma A, Kumar L. Cancer of the cervix: What is better? Natl Med J India. 2018;31(2):97–8.

    Article  Google Scholar 

  5. Chopra SJ, Mathew A, Maheshwari A, Bhatla N, Singh S, Rai B, et al. National Cancer Grid of India Consensus Guidelines on the Management of Cervical Cancer. J Glob Oncol. 2018;4:1–15.

    PubMed  Google Scholar 

  6. Indian Council of Medical Research: Consensus document for the management of cancer cervix. 2016. https://www.icmr.nic.in/sites/default/files/reports/Cervix%2520Cancer.pdf. Accessed 03 Jan 2020.

  7. Bumrungthai S, Munjal K, Nandekar S, Cooper K, Ekalaksananan T, Pientong C, et al. Epidermal growth factor receptor pathway mutation and expression profiles in cervical squamous cell carcinoma: therapeutic implications. J Transl Med. 2015;13:244.

    Article  Google Scholar 

  8. Viswanath L, Naveen T, Siddanna P, Chetana P, Geethasree M, Sridhar P, et al. Epidermal growth factor receptor (EGFR) overexpression in patients with advanced cervical cancer. J Clin Oncol. 2014;32(15):e16538.

    Article  Google Scholar 

  9. Yadav SK, Verma A, Sarin N, Singh S. Expression of epidermal growth factor receptor in squamous cell carcinoma of uterine cervix. Clin Cancer Investig J. 2019;8:227–31.

    CAS  Article  Google Scholar 

  10. Soonthornthum T, Arias-Pulido H, Joste N, Lomo L, Muller C, Rutledge T, et al. Epidermal growth factor receptor as a biomarker for cervical cancer. Ann Oncol. 2011;22(10):2166–78.

    CAS  Article  Google Scholar 

  11. Patil VM, Noronha V, Joshi A, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al. A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer. Cancer. 2019;125(18):3184–97.

    CAS  Article  Google Scholar 

  12. Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL III, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999;340(15):1154–61.

    CAS  Article  Google Scholar 

  13. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340(15):1144–53.

    CAS  Article  Google Scholar 

  14. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340(15):1137–43.

    CAS  Article  Google Scholar 

  15. Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999;17(5):1339–488.

    CAS  Article  Google Scholar 

  16. Peters WA III, Liu PY, Barrett RJ II, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18(8):1606–13.

    CAS  Article  Google Scholar 

  17. Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, et al. Cisplatin chemoradiotherapy vs radiotherapy in FIGO stage IIIB squamous cell carcinoma of the uterine cervix: a randomized clinical trial. JAMA Oncol. 2018;4(4):506–13.

    Article  Google Scholar 

  18. Kirwan JM, Symonds P, Green JA, Tierney J, Collingwood M, Williams CJ. A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer. Radiother Oncol. 2003;68(3):217–26.

    Article  Google Scholar 

  19. Nogueira-Rodrigues A, Moralez G, Grazziotin R, Carmo CC, Small IA, Alves FV, et al. Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer. Cancer. 2014;120(8):1187–93.

    CAS  Article  Google Scholar 

  20. Rawat S, Advait MK, Mandloi P. Comparative evaluation of radiotherapy with concurrent weekly cisplatin versus concurrent daily erlotinib and weekly cisplatin in locally advanced carcinoma cervix. Int J Sci Stud. 2017. https://doi.org/10.18535/jmscr/v6i12.181.

    Article  Google Scholar 

  21. Rawat S, Mandloi P. The comparative study in locally advanced carcinoma cervix with radiotherapy and concurrent weekly cisplatin versus concurrent daily Erlotinib & weekly Cisplatin an extended follow up study. IOSR J Dent Med Sci. 2018;17(3):79–85.

    Google Scholar 

  22. Benson R, Pathy S, Kumar L, Mathur S, Pandey R, Chander S, et al. Early clinical results of a phase II trial evaluating neoadjuvant chemotherapy followed by chemoradiation and maintenance gefitinib in locally advanced cervical cancer. J Clin Oncol. 2016;34(15):e17014.

    Article  Google Scholar 

  23. Monk BJ, Mas Lopez L, Zarba JJ, Oaknin A, Tarpin C, Termrungruanglert W, et al. Phase II, open-label study of Pazopanib or Lapatinib monotherapy compared with Pazopanib Plus Lapatinib combination therapy in patients with advanced and recurrent cervical cancer. J Clin Oncol. 2010;28(22):3562–9.

    CAS  Article  Google Scholar 

  24. Qureshi R, Arora H, Biswas S, Perwez A, Naseem A, Wajid S, et al. Mutation analysis of EGFR and its correlation with the HPV in Indian cervical cancer patients. Tumour Biol. 2016;37(7):9089–98.

    CAS  Article  Google Scholar 

  25. Moore KN, Sill MW, Miller DS, McCourt C, De Geest K, Rose PG, et al. A phase I trial of tailored radiation therapy with concomitant cetuximab and cisplatin in the treatment of patients with cervical cancer: a gynecologic oncology group study. Gynecol Oncol. 2012;127(3):456–61.

    CAS  Article  Google Scholar 

  26. Scholl SME, De la Rochefordiere A, Petrow P, Floquet A, Petit T, Alran S, et al. CETUXICOL, a phase II trial randomizing standard treatment with or without cetuximab in primary cervical cancer treatment. J Clin Oncol. 2012;30(15):e15535.

    Article  Google Scholar 

  27. De la Rochefordiere A, Kamal M, Floquet A, Thomas L, Petrow P, Petit T, et al. PIK3CA pathway mutations predictive of poor response following standard radiochemotherapy ± cetuximab in cervical cancer patients. Clin Cancer Res. 2015;21(11):2530–7.

    Article  Google Scholar 

  28. Qu A, Wang J, Jiang P, Wang P, Zhang M, Li X, et al. Safety and efficacy of nimotuzumab and concurrent intensity-modulated radiation therapy and chemotherapy for locally advanced cervical squamous cell cancer. J Clin Oncol. 2019;37(15):5532.

    Article  Google Scholar 

  29. Chen YF, Tang WB, Pan XX, Wu CR, Cao Y, Yang W. Safety and efficacy of nimotuzumab combined with chemoradiotherapy in Chinese patients with locally advanced cervical cancer. Onco Targets Ther. 2017;10:4113–9.

    Article  Google Scholar 

  30. Chen W, Li T, Wang J, Liang L, Huang D, Yan G, et al. Clinical study of nimotuzumab combined with concurrent radiochemotherapy for treatment of locally advanced cervical cancer. Cancer Manag Res. 2019;11:8157–65.

    CAS  Article  Google Scholar 

  31. Cao Y, Deng L, Lian S, Jiang Y. Research on the efficacy of cisplatin and nimotuzumab combined with concurrent chemoradiotherapy on locally advanced cervical cancer. J Buon. 2019;24(5):2013–9.

    PubMed  Google Scholar 

  32. Rawat S. Nimotuzumab in the Management of Carcinoma of Cervix. Gynecol Obstet Case Rep. 2018;4(3):67.

    Article  Google Scholar 

Download references

Funding

No funds were received for this study.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, NSCB Medical College and Government Cancer Hospital, Jabalpur, Madhya Pradesh, India

    Shyam Ji Rawat & Rajesh Jain

  2. Biocon Biologics India Limited, Bangalore, Karnataka, India

    Ramez Ahmed

Authors
  1. Shyam Ji Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajesh Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ramez Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shyam Ji Rawat.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rawat, S.J., Jain, R. & Ahmed, R. Nimotuzumab with Concurrent Chemoradiation in the Treatment of Locally Advanced Cervical Cancer: A Single-Centre Experience. Indian J Gynecol Oncolog 18, 92 (2020). https://doi.org/10.1007/s40944-020-00439-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40944-020-00439-y

Keywords

  • Nimotuzumab
  • Concurrent
  • Chemoradiation
  • Cervical
  • Locally advanced
  • EGFR