Elsevier

Cancer/Radiothérapie

Volume 16, Issue 7, October 2012, Pages 601-603
Cancer/Radiothérapie

Original article
Radiotherapy combined with cetuximab for locally advanced head and neck cancer: Results and toxicityAssociation radiothérapie–cétuximab chez des patients atteints d’un carcinome épidermoïde ORL localement évolué non opérable : résultats et effets secondaires

https://doi.org/10.1016/j.canrad.2012.06.005Get rights and content

Abstract

Purpose

To describe the clinical results and tolerance of the combined treatment with radiotherapy and cetuximab for locally advanced head and neck cancer.

Patients and methods

From August 2006 and October 2010, 36 patients with advanced squamous cell head and neck carcinoma were treated with radiotherapy (70 Gy/35 fractions) and cetuximab (400 mg/m2 one week before radiotherapy, following by 250 mg/m2 once weekly, until week 7 of radiotherapy). Tolerance was evaluated every week. All patients were examined every 3 months the first 3 years after therapy, and then every year.

Results

The median follow-up was 14 months. The majority of patients were male (31 out of 36). Mean age was 59 years. The tumours sites were: oral cavity (n = 8); oropharynx (n = 15); hypopharynx (n = 5); larynx (n = 8). Ninety percent of tumors were T3 or T4, and 45% were N2 or N3. Complete response was seen in 74% of patients, partial response in 17% and no response in 9% of patients. The overall survival was 44.4%. Relapse occurred in six patients. Anaphylactic reaction during the first infusion of cetuximab was observed in one patient. One patient developed severe aplasia after 48 Gy and 5 weeks of cetuximab, and died of sepsis. Eighty percent of patients presented acne, 16 patients developed a mucositis grade 2–3 and 23 patients a grade 2 skin reaction.

Conclusion

The concomitant use of cetuximab and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. The results seem comparable to those in the literature.

Résumé

Objectif de l’étude

Décrire les résultats cliniques et la tolérance d’un traitement par irradiation et cetuximab (Erbitux®) chez des patients atteints de carcinome épidermoïde de la sphère ORL localement évolué.

Patients et méthodes

D’août 2006 au octobre 2008, 36 patients atteints d’un carcinome épidermoïde évolué de la sphère ORL de stade IV non métastatique ont bénéficié d’une association de radiothérapie de 70 Gy en 35 séances et de cetuximab (400 mg/m2 la semaine précédant la radiothérapie puis 250 mg/m2 chaque semaine de la radiothérapie). La tolérance a été évaluée chaque semaine. Tous les patients ont été examinés tous les trois mois les trois premières années après le traitement, puis tous les ans.

Résultats

Le suivi médian était 14 mois. La majorité des patients étaient de sexe masculin (31 sur 36). L’âge moyen était de 59 ans. La localisation tumorale était la cavité buccale pour huit patients, l’oropharynx pour 15, l’hypopharynx pour cinq et le larynx pour huit. Quatre-vingt-dix pour cent des tumeurs étaient de stade T3 ou T4, et 45 % N2 ou N3. Une réponse complète a été observée chez 74 % des patients, une réponse partielle chez 17 % et pas de réponse dans 9 % des patients. La probabilité de survie globale était de 44,4 %. Une rechute est survenue chez six patients. Une réaction anaphylactique au cours de la première perfusion du cetuximab a été observée chez un patient. Un patient a souffert d’une aplasie sévère après 48 Gy et cinq semaines de cetuximab, et est décédé d’une septicémie. Quatre-vingt pour cent des patients ont été atteints d’acné, 16 d’une mucite de grade 2–3 et 23 d’une réaction cutanée de grade 2.

Conclusion

Notre étude montre une bonne tolérance au traitement associant radiothérapie et cetuximab. Les résultats semblent comparables à ceux publiés dans la littérature.

Introduction

Head and neck cancers are the sixth most common solid malignancies worldwide and are related to 350,000 deaths worldwide every year [1]. Most (90–95%) of head and neck cancers are squamous cell carcinomas (HNSCC). The most important risk factors for HNSCC are tobacco abuse and alcohol consumption, implicated in 75% of all HNSCC [1]. Recently, the human papillomavirus (HPV) infection has been implicated [2].

The management of patients with HNSCC is complex, owing to the heterogeneity of this disease [2].

Traditionally, the patients’ managing with HNSCC has been surgical. Gradually the radio-chemotherapy has been included as an option, searching increased survival, curability, organ preservation and quality of life [3], [4].

Knowledge of new molecules implicated in the cancer pathogenesis has led to the development of new therapeutic strategies. Between these, epidermal growth factor (EGF) has been described as an interesting target. The EGF receptor (EGFR) is a transmembrane glycoprotein possessing tyrosine kinase activity. The EGFR is abnormally activated in HNSCC, and overexpression of this receptor is associated with more aggressive disease [3].

Cetuximab is a chimeric human-murin immunoglobulin G1 monoclonal antibody highly selective for the EGFR [5].

Here we described the clinical results and tolerance of the combined treatment with radiotherapy and cetuximab in 36 HNSCC patients treated in the department of radiotherapy at the Brest University, France.

Section snippets

Patients and methods

Thirty-six HNSCC patients treated between August 2006 and October 2010 with combination of radiotherapy and cetuximab in the radiotherapy department of the Brest Universitary Hospital, France, were retrospectively reviewed. Treatment tolerance and response were analyzed.

The patients were evaluated with endoscope, head and neck computed tomography (CT) and PET-scanner. Metastasis were not found. No prior treatment had been carried out. A gastrostomy was made in 22 patients. All patients

Statistical analysis

Survival and control response probabilities were calculated from the day of the end of radiotherapy. The results are expressed as mean ± standard deviation. Comparisons between means were performed by Mann-Whitney U test. The Kaplan-Meier method was used to determine overall survival (OS) and disease-free survival.

Results

Thirty-six HNSCC patients were treated with combined radiotherapy and cetuximab. All patients were available for assessment of tumour response, toxicity and disease-free survival. The median follow-up was 14 months. The majority of patients were male (31/36). Mean age was 59 years. Smoking history was present in 97% of cases, and alcohol consumption in 62% of patients. The tumours sites were the oral cavity (n = 8); oropharynx (n = 15); hypopharynx (n = 5); larynx (n = 8). Ninety percent were T3 or T4,

Follow-up

All patients were examined every 3 months the first 3 years after therapy, and then every year. They underwent clinical ENT-examination including magnifying laryngoscopy, ultrasound, PET-scan and/or a CT of the head and neck region if indicated.

Response and recurrence

The complete response was defined as the absence of recurrent disease above the clavicles and partial response as a decrease in the size of tumor and/or lymph node and was evaluated 2 months following the radiotherapy by clinical examination and CT scans. Complete response was seen in 74% of patients, partial response in 17% and no response in 9% of patients.

Death has occurred in 20 patients. In each case, the patient either died from carcinoma or had active disease at the time of death. OS was

Toxicity

Anaphylactic reaction during the first infusion of cetuximab was observed in one patient. One patient developed severe aplasia the fifth week of cetuximab, and died of sepsis. Eighty percent of patients presented acne.

Acute toxicity is listed in Table 2. During treatment 16/36 patients developed a mucositis grade 2–3. Two patients were hospitalised for 14 and 20 days secondary to a lung infection, 1 patient was rested for 17 days owing to acute respiratory distress syndrome requiring

Discussion

The most important goal in HNSCC treatment is to achieve locoregional control. To try to improve the results of treatment of HNSCC, several approaches have been used over the years. Although many patients will develop distant metastases, locoregional control of tumours remains the major problem. Surgery and radiotherapy remain the main methods of treatment. Multiple clinical trials have demonstrated the ability of concurrent chemo-radiotherapy to improve survival [6].

However, the goal is not

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Authors’ contributions: C.A. reviewed the patient data and drafted the manuscript. G.V., P.M. and E.L. helped the draft of the manuscript. O.P. participated in its concept design and helped the draft of the manuscript. All authors read and approved the final manuscript.

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