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Year : 2011  |  Volume : 48  |  Issue : 2  |  Page : 154--157

Cetuximab plus radiotherapy in patients with unresectable locally advanced squamous cell carcinoma of head and neck region - A open labelled single arm phase II study

S Dattatreya1, C Goswami2,  
1 Department of Medical Oncology, Omega Hospital, Banjara Hills, Hyderabad, Andhra Pradesh, India
2 BP Poddar Hospital, New Alipore, Kolkata, India

Correspondence Address:
S Dattatreya
Department of Medical Oncology, Omega Hospital, Banjara Hills, Hyderabad, Andhra Pradesh
India

Abstract

Purpose : To evaluate feasibility, safety and outcome of cetuximab concurrent with radiotherapy in locally advanced head−neck cancer. Materials and Methods: Between March 2007 and January 2008 eligible cases of locally advanced unresectable (Stage IV) squamous cell carcinoma of head and neck were enrolled in this single arm, open labeled phase II Study. They were treated with cetuximab for a duration of 8 weeks and concomitant RT for 7 weeks (starting one week after initiating Cetuximab) Results: A total of 19 eligible patients were enrolled. The median age of patients was 53 years, all patients happening to be male. The performance status of the patients was 0/1. The location of the primary tumor was oropharynx in 12 cases, oral cavity in 4, larynx in 2, and hypopharynx in one case. The overall response rate (ORR) was 68.42% and the overall survival at 2 year was 84 %. All 13 patients who completed two years follow-up after completion of study treatment continued to be alive with no evidence of disease progression. One patient also remained alive with progressive disease. Conclusions: Cetuximab concurrent with radiotherapy is a safe and effective option in advanced head−neck cancer patients.



How to cite this article:
Dattatreya S, Goswami C. Cetuximab plus radiotherapy in patients with unresectable locally advanced squamous cell carcinoma of head and neck region - A open labelled single arm phase II study.Indian J Cancer 2011;48:154-157


How to cite this URL:
Dattatreya S, Goswami C. Cetuximab plus radiotherapy in patients with unresectable locally advanced squamous cell carcinoma of head and neck region - A open labelled single arm phase II study. Indian J Cancer [serial online] 2011 [cited 2021 Jan 18 ];48:154-157
Available from: https://www.indianjcancer.com/text.asp?2011/48/2/154/82873


Full Text

 Introduction



Squamous cell carcinoma of the head and neck (SCCHN) is the most common cancer in India, and it also contributes significantly to cancer-related morbidity and mortality in developing countries. [1] In India, estimated 135,000 cases of SCCHN were newly diagnosed and 140,000 deaths in 2002 (GLOBOCAN 2002, IARC). [1] For patients who cannot be resected, concomitant radiotherapy (RT) is the standard of care. With the advent of targeted therapy, interest in the use of monoclonal antibodies has increased exponentially. Since the epidermal growth factor receptor (EGFR) gene is actively expressed in almost all SCCHN, cetuximab is the focus of our study - based on recently published encouraging published literature. [2],[3] We therefore present preliminary analysis of feasibility, safety, and outcome using cetuximab concurrent with radiotherapy in advanced SCCHN.

 Materials and Methods



The primary objectives of this study were to determine the safety and toxicity of cetuximab in combination with radiation in patients with locally advanced SCCHN. The secondary objectives included response rate, duration of response, time to progression, and loco-regional control at end of 2 years.

Eligible patients were enrolled into the study after taking informed consent.

The study medication consisted of Cetuximab 400 mg/m 2 in week 1 followed by 250 mg/m 2 from weeks 2 to 8. This was administered alongwith concomitant radiotherapy from week 2 to 8 (200 cGy per fraction five days a week for 7 weeks totaling 70Gy) [Figure 1].{Figure 1}

Following the initial 8 weeks of treatment, patients were followed up monthly for first three months, and then 3 monthly for two years. The safety and efficacy analysis were performed on the ITT population. NCI-CTC criteria were used to measure toxicity and RECIST criteria to measure response. Statistical analysis was not done due to small number of patients studied.

 Results



A total of 19 patients could be enrolled into the study. Their demographic features are shown in [Table 1]. All enrolled patients were males with a median age of 53 years. All of them had stage IVA disease. Their performance status was good and the median body surface area (BSA) was 1.53 m 2 . The location of the primary tumor was oropharynx in 12 cases, oral cavity in 4, larynx in 2, and hypopharynx in one case.{Table 1}

The planned dose intensity of RT (2 Gy/fraction) was maintained in 12 of the 19 enrolled patients [Table 2]. Eighteen of the enrolled patients completed the planned dosage of Cetuximab (one patient discontinued treatment owing to disease progression while on treatment). {Table 2}

A total of 4 patients achieved complete response (CR), 9 had partial response (PR), 4 had stable disease (SD), and 2 developed progressive disease (PD). Thus, the overall response rate (ORR) was 68.42% (13/19 patients; [Table 2]), and disease control rate (DCR) was 89.47% (17/19). The response rate among the various tumor sites was as follows: Oropharynx 3 CR, 4 PR, 3 SD, 2 PD; Oral cavity CR 1, PR 2, SD 1; larynx both had PR; patient with primary in hypopharynx also achieved a PR.

Of the two patients with progressive disease, one developed this while on treatment and the other showed disease progression two months after completion of study treatment. A total of two patients were lost to follow-up without progressive disease (at the 5 th and 6 th follow up visit, respectively).

There were no grade 3/4 adverse events (AEs; [Table 3]). A total of 7 patients had grade 1 and one patient had grade 2 dermatitis. Mucositis of grade 1 was seen in 10 patients. The patient with grade 2 dermatitis also developed post irradiation pigmentation and dry desquamation, 4 weeks after completion of treatment. {Table 3}

All the 13 patients achiving CR or PR continued to be alive and without disease progression at two years. At time of analysis, there were three patients lost to follow-up and the remaining 16 patients continued to remain alive (including the patients who had documented PD), giving an overall survival (OS) rate of 84% at two years.

 Discussion



Bonner et al were the first to show conclusively that the concurrent addition of cetuximab to RT significantly improved loco-regional control (34% vs 47%) and overall survival (45% vs 55%) at -three years. [4] Subsequent publications confirmed the 9% absolute survival benefit at five years. [5] However, the combination is not without significant toxicity - some authors raising the caution of significant skin reactions and rash. It is well known that toxicity can compromise the dose intensity, concomitant chemoradiotherapy, being unsuitable/ interrupted in as many as 30% of patients. [6]

This prompted us to evaluate its feasibility, safety, and efficacy of cetuximab and RT in patients from India. The OR rate (ORR) in our preliminary study seems to be similar to what is seen in the randomised phase III trial, while the two year locoregional control appears to be higher than that seen in the same study. [6]

Thus our phase II single arm study in patients from India supports similar findings in Caucasian patients.

We therefore conclude that the combination of Cetuximab with RT is a safe and feasible treatment protocol in Performance status 0 to 1 patients with unresectable locally advanced SCCHN. It is now necessary to compare this to concomitant chemoradiotherapy as well as combination of all three modalities (RT, chemotherapy, and monoclonal antibodies).

References

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2Zimmermann M, Zouhair A, Azria D, Ozsahin M. The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat Oncol 2006;1:11.
3Baselga J. The EGFR as a target for anticancer therapy--focus on cetuximab. Eur J Cancer 2001;37(Suppl 4):S16-S22.
4Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78.
5Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010;11:21-8.
6Giro C, Berger B, Bolke E, Ciernik IF, Duprez F, Locati L, et al. High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes. Radiother Oncol 2009;90:166-71.