Docetaxel in the management of patients with head and neck squamous cell carcinoma

The taxanes play a significant role in the treatment of various solid tumors of epithelial origin. Docetaxel is the most extensively studied taxane in prospective head and neck cancer trials and has been investigated as induction chemotherapy or in combination with radiotherapy in locally advanced squamous cell carcinomas of the head and neck (HNSCC) and as palliation in recurrent or metastatic disease. The data in locally advanced disease are particularly compelling. Three recently reported randomized trials, carried out in patients with locally advanced disease who were receiving induction chemotherapy followed by radiotherapy or chemoradiotherapy, demonstrated that adding docetaxel to the standard induction regimen of cisplatin/5-fluorouracil (PF) significantly improved survival compared with PF alone, without significantly increasing toxicity. On the basis of these trials, docetaxel/PF (TPF) has become the current standard induction regimen and TPF-based sequential therapy can be considered a standard treatment alternative to chemoradiotherapy alone in patients with locally advanced HNSCC. This review article discusses the current developments of docetaxel-based chemotherapy and the optimal use of this agent in patients with HNSCC.     

Gamma-delta T-cells in patients with squamous cell carcinoma of the head and neck

In our attempt to characterize a general immune-suppression found in patients with squamous cell carcinoma of the head and neck (SCCHN) we now focused on a subset of CD3 lymphocytes described as gamma/delta-T-cells, a cell type with potential relevance in non-MHC restricted anti-tumor immune responses. Peripheral blood of 33 SCCHN patients and 33 age-matched controls (CON) was evaluated for the frequency of gamma/delta-T-cells among CD3+ T-cells and their onset of apoptosis (Annexin V binding) by multicolor flow cytometry. Results were correlated with clinical parameters. Patients with SCCHN had a significantly higher proportion of gamma/delta-T-cells compared to healthy controls (4.4+/-0.4% for SCCHN vs. 3.0+/-0.3% for CON, p=0.01). However, this increase was not paralleled with a difference in the onset of apoptosis if compared to CON. There was also no correlation between the proportion of gamma/delta-T-cells and tumor stage. However, a significantly higher proportion of gamma/delta-T-cells was found in patients with recurrent or metachronous second primary SCCHN (6.0+/-1.0%) if compared to the other SCCHN (3.8+/-0.4%, p=0.02). In a follow up 3-6 months post-treatment patients showed a decrease of gamma/delta-T-cells among CD3+cells (2.7+/-0.4%, n=4) if they were operated only and an increase if primary radio-chemotherapy (6.7+/-1.7%, n=8) or a combination of operation plus radio-chemotherapy (6.8+/-2.3%, n=3) was applied. Furthermore, patients receiving palliative treatment including radio-chemotherapy had highest values of gamma/delta-T-cells (9.1+/-2.7%, n=4) overall implicating that the treatment modality significantly influences the proportion of gamma/delta-T-cells. Since patients with SCCHN, particularly those with recurrent or second primary disease after treatment, had a higher proportion of gamma/delta-T-cells without signs of a reduced onset of apoptosis this could be due to an increased de novo generation. The current study implies that increased frequencies of gamma/delta-T-cells in patients with SCCHN may not only be the result of tumor-host interactions but the consequence of applied treatment modalities.     

Docetaxel in the management of patients with head and neck squamous cell carcinoma

The taxanes play a significant role in the treatment of various solid tumors of epithelial origin. Docetaxel is the most extensively studied taxane in prospective head and neck cancer trials and has been investigated as induction chemotherapy or in combination with radiotherapy in locally advanced squamous cell carcinomas of the head and neck (HNSCC) and as palliation in recurrent or metastatic disease. The data in locally advanced disease are particularly compelling. Three recently reported randomized trials, carried out in patients with locally advanced disease who were receiving induction chemotherapy followed by radiotherapy or chemoradiotherapy, demonstrated that adding docetaxel to the standard induction regimen of cisplatin/5-fluorouracil (PF) significantly improved survival compared with PF alone, without significantly increasing toxicity. On the basis of these trials, docetaxel/PF (TPF) has become the current standard induction regimen and TPF-based sequential therapy can be considered a standard treatment alternative to chemoradiotherapy alone in patients with locally advanced HNSCC. This review article discusses the current developments of docetaxel-based chemotherapy and the optimal use of this agent in patients with HNSCC.     

Human papillomavirus status in young patients with head and neck squamous cell carcinoma

The role of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) development has been recognized only in the last decade. Although younger patients develop HNSCC associated with HPV, the incidence in young patients has not been studied. Forty-five young HNSCC patients (<40 years) were tested for HPV and the expression of p16(ink4a) and p53 in tumor biopsies. The presence of HPV was correlated with the absence and presence of alcohol and tobacco exposure. Paraffin-embedded, archival biopsy materials from HNSCC of 45 patients younger than 40 years were analyzed. HPV subtypes were identified by PCR followed by genotyping. Expression of p16(ink4a) and p53 were determined by immunohistochemistry. Fourteen (31%) of the HNSCC specimens from 45 patients unequivocally exhibited HPV16 positivity. Sixty percentage of the oropharyngeal tumors and 5% of the oral cavity tumors were HPV16 positive. P16(ink4a) overexpression was detected in 93% of the HPV16-positive tumors. None of the HPV16 tumors showed p53 overexpression. There was no association of HPV positivity with (lack of) exposure to alcohol and smoking. HPV association was not exclusively detected in nonsmoking, nondrinking young HNSCC patients. The presence of p16(ink4a) accumulation and the absence of p53 overexpression are good surrogate markers for HPV-associated HNSCC.     

Treatment patterns in older patients with locally advanced head and neck squamous cell carcinoma: Results from an EORTC led survey

ObjectivesWe aimed to assess patterns of care delivered to older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), and to analyze the use of geriatric assessment (GA) and assessment of quality of life (QoL).Materials and methodsMembers of the head and neck cancer group and the older task force of the European Organisation for Research and Treatment of Cancer (EORTC), members the European Head and Neck Society and members of national groups in Europe were asked to complete a questionnaire about treatment delivered, use of GA, and QoL assessment in older patients with LA-HNSCC.ResultsInvestigators from 111 centers replied, including 90 (81.1%) academic centers, 16 (14.4%) community hospitals, and 5 (4.5%) private clinics. Large differences in treatment patterns were found. For instance, for oropharyngeal carcinoma, one third of the centers indicated that they treat <5% of older patients with chemoradiation, while 18 centers (16.2%) treat >40% of older patients with chemoradiation. Fourteen centers (12.6%) routinely perform GA, while 43 centers (38.7%) never do, and 39 centers (35.1%) sometimes do. QoL is assessed on a routine basis in one fifth of the centers.ConclusionsLarge differences exist across institutions in the patterns of care delivered to older patients with LA-HNSCC. Prospective studies are required to learn how GA can guide treatment decisions, and how QoL and treatment outcome can be improved. For that, consensus on standard of care is essential.     

Nivolumab in squamous cell carcinoma of the head and neck

Introduction: The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC.

Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC.

Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines.     

Cetuximab in squamous cell carcinoma of the head and neck

Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemotherapy and chemoradiotherapy are new alternatives for locally advanced disease, particularly induction chemotherapy for patients with unresectable tumors. In recurrent/metastatic disease and after progression to platin-based regimens, no treatments other than best supportive care are currently available. Most SCCHN tumors overexpress the epidermal growth factor receptor (EGFR). This is a tyrosine kinase membrane receptor and has a clear implication in angiogenesis, tumor progression and resistance to different cancer treatments. Cetuximab is a monoclonal antibody that binds to EGFR and alters the tyrosine kinase-mediated signal transduction pathway. The drug is active in colon cancer and is currently being tested in SCCHN patients. For locally advanced disease, cetuximab/radiotherapy combination has demonstrated a benefit in survival when compared with radiotherapy alone as radical treatment. Cetuximab is an active treatment in platin-refractory patients with recurrent/metastatic disease.     

老年头颈部鳞状细胞癌患者的治疗耐受性及预后情况分析

目的 探讨老年头颈部鳞状细胞癌(HNSCC)患者的治疗耐受性及预后情况.方法 选取42例老年HNSCC患者,采用Cox比例风险回归模型分析其治疗耐受性和不良反应的影响因素,分析导致其治疗中断的根本原因,并对相关因素进行生存分析.结果 不同临床症状老年HNSCC患者原发灶位置比较,差异均有统计学意义(P﹤0.05),其中喉癌患者发生疼痛、吞咽困难和口腔黏膜炎的风险最低(P﹤0.05);美国东部肿瘤协作组(ECOG)体力状况(PS)评分为3～4分患者发生疼痛和吞咽困难的风险较高,而发生口腔黏膜炎的风险较低(P﹤0.05);年龄校正的查尔森合并症指数(aCCI)评分﹥8分的患者发生吞咽困难的风险最高,口腔黏膜炎的风险最低(P﹤0.01);TNM分期为Ⅲ～Ⅳ期的患者发生疼痛、吞咽困难、口腔黏膜炎的风险均较高(P﹤0.05).不同ECOG评分、原发灶位置、TNM分期、治疗方式的选择、治疗中断情况老年HNSCC患者伴或不伴合并症比较,差异均有统计学意义(P﹤0.05).不同治疗中断情况老年HNSCC患者的PFS比较,差异有统计学意义(HR=2.406,95％CI:0.977～5.925,P=0.042);伴或不伴合并症老年HNSCC患者的PFS比较,差异无统计学意义(P﹥0.05).结论 伴有合并症的老年HNSCC患者具有更高的ECOG评分,晚期患者更容易发生各类严重合并症,导致治疗耐受性差,不良反应的发生风险增高,进一步导致治疗中断而造成预后不良.