Reirradiation with cetuximab in locoregional recurrent and inoperable squamous cell carcinoma of the head and neck: feasibility and first efficacy results.
ABSTRACT To report our experience with a prospective protocol of external beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable, recurrent squamous cell carcinoma of the head and neck (SCCHN).
Between August 2008 and June 2010, 18 patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were enrolled. Acute and late toxicity from the experimental regimen were recorded every week during RT and every 3 months thereafter. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors and clinical examinations 8-12 weeks after completion of the treatment and every 3 months thereafter.
Median follow-up time for all patients was 9.4 (range: 3.85-31.7) months and for patients alive 30.4 (range: 15.7-31.7) months. Acute toxicity was generally mild or moderate. Five patients developed a grade 3 acneiform rash related to cetuximab. Late toxicity occurred as grade 3 trismus in five and as grade 3 abacterial salivary gland inflammation in one patient, respectively. Overall response rate was 47%. Median overall and progression-free survival for all patients was 8.38 months and 7.33 months, respectively. The overall survival rate was 44% at 1 year, with a 1 year local control rate of 33%.
Notwithstanding the limitations of our preliminary data Re-RT combined with cetuximab for recurrent and inoperable SCCHN is feasible and the integration of newer targeted agents seems to be less toxic compared to conventional chemotherapy with encouraging response rates at least for a subset of patients.
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ABSTRACT: The multidisciplinary approach is becoming the standard for treatment of advanced head and neck cancer. Combined modality treatment preserves quality of life as well as improving the length of survival time. Molecular targeted drugs have become very important in the multidisciplinary approach for the treatment of advanced head and neck cancer. Cetuximab has been shown to have locoregional control and additional survival benefits in locally advanced squamous cell carcinoma of the head and neck as well as additional survival benefits in distant metastatic/recurrent squamous cell carcinoma of the head and neck. Recently, many clinical studies of the multidisciplinary approach including cetuximab have been carried out in Europe and the US. It has been shown that cetuximab in combination with radiotherapy (RT) is significantly superior to the RT alone in median locoregional control duration and median overall survival (OS). For recurrent or metastatic disease, the results of a phase III randomized control study of CDDP + 5-fluorouracil combination therapy with or without cetuximab reported that OS was significantly longer with than without cetuximab, demonstrating an additional survival benefit of cetuximab. Many trials including induction chemotherapy are being conducted. Clinical trials with cetuximab have also been conducted in Japan. Though combination with cetuximab shows some benefit, further studies are necessary to obtain the standard treatments for a multidisciplinary approach for advanced head and neck cancer.International Journal of Clinical Oncology 02/2014; · 1.41 Impact Factor
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ABSTRACT: For some patients with recurrent, unresectable, and previously irradiated head and neck squamous cell carcinoma (HNSCC), reirradiation (re-RT) may be a curative option. Chemotherapy with epidermal growth factor receptor (EGFR) inhibition is established as palliative management. This retrospective single-institutional study investigates feasibility, toxicity, and outcome of reirradiation (re-RT) combined with EGFR blockade for these patients.Between June 2008 and June 2012, 23 patients with inoperable and previously irradiated HNSCC were reirradiated. Concomitant EGFR blockade (cetuximab) was given initially at 400 mg/m2 two days prior to re-RT and weekly (250 mg/m2) thereafter. PET/CT imaging was fused with planning CT in 8 patients.One patient died of anaphylactic shock during the first cetuximab administration; two discontinued treatment on their own request. In all, 20 patients completed re-RT (50.4–66.6 Gy) and received cetuximab as prescribed. Grade 3 acute side effects were documented for dermatitis (35 %), dysphagia (30 %), acneiform rash (30 %), and mucositis (15 %). The 1-year overall survival rate was 34.8 %. Median overall and progression-free survival times were 9 and 4.3 months, respectively. A multivariable analysis using the Cox regression model showed significant positive impact of acneiform rash (hazard ratio [HR] 0.1531, 95 % confidence interval [CI] 0.0383–0.6111), while a period from first radiation to re-RT longer than 120 months negatively (HR 0.1633, 95 % CI 0.0305–0.8734) influenced patient survival.re-RT with concurrent cetuximab was feasible. Compared to platinum-based chemotherapy with fluorouracil and cetuximab, this therapeutic approach did not demonstrate survival benefit. Prolonged intervals from first treatment to re-RT seem to be unfavorable.Strahlentherapie und Onkologie 01/2013; 189(10). · 4.16 Impact Factor
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ABSTRACT: Local and/or regional recurrence and metachronous primary tumor arising in a previously irradiated area are rather frequent events in patients with head and neck squamous cell carcinoma (HNSCC). Re-treatment is associated with an increased risk of serious toxicity and impaired quality of life (QOL) with an uncertain survival advantage. We analyzed the literature on the efficacy and toxicity of photon/electron-based external beam reirradiation for previously irradiated patients with HNSCC of non-nasopharyngeal origin. Studies were grouped according to the radiotherapy technique used for reirradiation. Patient selection criteria, target volume identification method, tumor dose, fractionation schedule, systemic therapy administration, and toxicities were reviewed. In addition to disease-related factors, current comorbidities and preexisting organ dysfunction must be considered when selecting patients for reirradiation. As morbidity from re-treatment may be considerable and differ depending on which mode of re-treatment is used, it is important to give patients information on potential morbidity outcomes so that an informed choice can be made within a shared decision-making context. With improved dose distribution and adequate imaging support, including positron emission tomography-CT, modern radiotherapy techniques may improve local control and reduce toxicity of reirradiation. A reirradiation dose of ≥60 Gy and a volume encompassing the gross tumor with up to a 5-mm margin are recommended. Concomitant administration of systemic therapeutics and reirradiation is likely to be of similar benefit as observed in large randomized studies of upfront therapy. Reirradiation, administered either with or without concurrent systemic therapy, is feasible and tolerable in properly selected patients with recurrent or a new primary tumor in a previously irradiated area of the head and neck, offering a meaningful survival (in the range of 10% to 30% at 2 years). Whenever feasible, salvage surgery is the method of choice for curative intent; patients at high-risk for local recurrence should be advised that postoperative reirradiation is expected to increase locoregional control at the expense of higher toxicity and without survival advantage compared to salvage surgery without reirradiation. © 2013 Wiley Periodicals, Inc. Head Neck, 2014.Head & Neck 11/2013; · 2.83 Impact Factor