Safety and efficacy of nimotuzumab with concurrent chemoradiotherapy in unresectable locally advanced squamous cell carcinoma of head and neck: An Indian rural hospital experience

Shyamji Rawat; Hemu Tandan; Sanandan Patel; Sameer Chaudhari

doi:10.4103/sajc.sajc_76_18

South Asian Journal of Cancer, Table of Contents

CC BY-NC-ND 4.0 · South Asian J Cancer 2019; 08(01): 52-56
DOI: 10.4103/sajc.sajc_76_18

ORIGINAL ARTICLE: Head and Neck Cancers

Safety and efficacy of nimotuzumab with concurrent chemoradiotherapy in unresectable locally advanced squamous cell carcinoma of head and neck: An Indian rural hospital experience

Shyamji Rawat

Department of Radiation Oncology, NSCB Medical College and Government Hospital, Jabalpur, Madhya Pradesh

,

Hemu Tandan

Department of Radiation Oncology, NSCB Medical College and Government Hospital, Jabalpur, Madhya Pradesh

,

Sanandan Patel

Department of Radiation Oncology, NSCB Medical College and Government Hospital, Jabalpur, Madhya Pradesh

,

Sameer Chaudhari

Department of Radiation Oncology, NSCB Medical College and Government Hospital, Jabalpur, Madhya Pradesh

› Author Affiliations

Abstract

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Abstract

Context: Nimotuzumab is the only anti-epidermal growth factor receptor monoclonal antibody which can be safely added to concurrent chemoradiotherapy (CRT) to improve efficacy in the management of unresectable, locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). However, the evidence available on this is limited. Aims: We retrospectively investigated efficacy and safety of nimotuzumab when combined with chemoradiation for LA-SCCHN. Settings and Design: Hospital records of 39 patients from January 2012 to December 2016 diagnosed with locally advanced (Stage III-IVb), unresectable SCCHN, and treated with concurrent CRT with weekly nimotuzumab were reviewed retrospectively after fulfilling the inclusion/exclusion criteria. Subjects and Methods: Tumor response was calculated as per response evaluation criteria in solid tumors criteria 1.1. Association of tumor response with independent variables was assessed. Overall survival (OS) and progression-free survival (PFS) were calculated. All patients were assessed for toxicity as per common terminology criteria for adverse events Common Terminology Criteria for Adverse Events v 4.0 (U.S. Department of health and human services, National Institutes of Health, National Cancer Institute). Results: At 6 months after completion of treatment, objective response rate was 97.44% with 26 (66.67%) patients attaining Complete response (CR), 12 (30.77%) patients with Partial response (PR), and one patient (2.56%) had stable disease. Subgroup analysis did not show a significant association of tumor response with independent factors. OS at 1 and 2-year was 100% and 72.9%, while PFS at 1 and 2-year was 87% and 54.40%. The incidence of Grade I, II, III, and IV toxicity was 30%, 18.18%, 41.82%, and 10%, respectively. No grade V toxicity was observed. Common adverse events observed were mucositis (33.64%), skin reaction (24.55%), neutropenia (20.91%), vomiting (18.18%), and diarrhea (2.73%). Conclusions: Nimotuzumab is an efficacious and safe option when added to concurrent CRT in unresectable, LA-SCCHN.

Key words

Advanced - antibodies - carcinoma - head and neck neoplasms - inoperable - Monoclonal - Nimotuzumab - Overall survival - squamous cell - therapy

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References

References
1 Dayal PK, Mani NJ, Bhargava K. Prevalence of oral cancer and precancerous lesions in 'pan'/'supari' chewers. Indian J Public Health 1978;22:234-45.
2 Joshi P, Dutta S, Chaturvedi P, Nair S. Head and neck cancers in developing countries. Rambam Maimonides Med J 2014;5:e0009.
3 Graham S, Dayal H, Rohrer T, Swanson M, Sultz H, Shedd D, et al. Dentition, diet, tobacco, and alcohol in the epidemiology of oral cancer. J Natl Cancer Inst 1977;59:1611-8.
4 Parikh P, Patil V, Agarwal JP, Chaturvedi P, Vaidya A, Rathod S, et al. Guidelines for treatment of recurrent or metastatic head and neck cancer. Indian J Cancer 2014;51:89-94.
5 Tuljapurkar V, Dhar H, Mishra A, Chakraborti S, Chaturvedi P, Pai PS, et al. The Indian scenario of head and neck oncology – Challenging the dogmas. South Asian J Cancer 2016;5:105-10.
6 Puram SV, Rocco JW. Molecular aspects of head and neck cancer therapy. Hematol Oncol Clin North Am 2015;29:971-92.
7 Pignon JP, le Maître A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14.
8 Agulnik M. New approaches to EGFR inhibition for locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN). Med Oncol 2012;29:2481-91.
9 Benson R, Mallick S, Julka PK, Rath GK. Anti EGFR therapy in the treatment of non-metastatic head and neck squamous cell carcinoma: The current evidence. J Egypt Natl Canc Inst 2016;28:141-8.
10 Qu YY, Hu SL, Xu XY, Wang RZ, Yu HY, Xu JY, et al. Nimotuzumab enhances the radiosensitivity of cancer cells in vitro by inhibiting radiation-induced DNA damage repair. PLoS One 2013;8:e70727.
11 Diaz-Miqueli A, Martinez GS. Nimotuzumab as a radiosensitizing agent in the treatment of high grade glioma: Challenges and opportunities. Onco Targets Ther 2013;6:931-42.
12 Psyrri A, Yu Z, Weinberger PM, Sasaki C, Haffty B, Camp R, et al. Quantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis. Clin Cancer Res 2005;11:5856-62.
13 Fan Z, Baselga J, Masui H, Mendelsohn J. Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 1993;53:4637-42.
14 Zhao L, Li QQ, Zhang R, Xi M, Liao YJ, Qian D, et al. The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin. Tumour Biol 2012;33:1115-23.
15 Pfister DG, Su YB, Kraus DH, Wolden SL, Lis E, Aliff TB, et al. Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: A pilot phase II study of a new combined-modality paradigm. J Clin Oncol 2006;24:1072-8.
16 Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol 2014;32:2940-50.
17 Reddy BK, Lokesh V, Vidyasagar MS, Shenoy K, Babu KG, Shenoy A, et al. Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: A randomized, open-label, phase IIb, 5-year study in Indian patients. Oral Oncol 2014;50:498-505.
18 Bhatnagar AR, Singh DP. A comparative study of monoclonal antibody against EGFR (nimotuzumab) used in combination with chemoradiation versus chemoradiation alone in the treatment of locally advanced inoperable squamous cell carcinoma of the head and neck. J Clin Oncol 2012;Suppl 30:e16012.
19 Somani N. Nimotuzumab with concurrent chemo-radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck. J Cancer Ther 2015;6:356-61.
20 Kumar A, Mishra KC. To assess the possibility of combining MAb (nimotuzumab) with concurrent chemoradiation in patients with locally advanced squamous cell carcinoma of head and neck. Scientific Abstracts. Indian J Med Paediatr Oncol 2012;33:1.
21 Wykosky J, Fenton T, Furnari F, Cavenee WK. Therapeutic targeting of epidermal growth factor receptor in human cancer: Successes and limitations. Chin J Cancer 2011;30:5-12.
22 Siu LL, Waldron JN, Chen BE, Winquist E, Wright JR, Nabid A, et al. Phase III randomized trial of standard fractionation radiotherapy (SFX) with concurrent cisplatin (CIS) versus accelerated fractionation radiotherapy (AFX) with panitumumab (PMab) in patients (pts) with locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN): NCIC Clinical Trials Group HN.6 trial. J Clin Oncol 2015;33(15_suppl):6000.
23 Perez R, Moreno E, Garrido G, Crombet T. EGFR-targeting as a biological therapy: Understanding nimotuzumab's clinical effects. Cancers (Basel) 2011;3:2014-31.
24 Garrido G, Tikhomirov IA, Rabasa A, Yang E, Gracia E, Iznaga N, et al. Bivalent binding by intermediate affinity of nimotuzumab: A contribution to explain antibody clinical profile. Cancer Biol Ther 2011;11:373-82.