Induction chemotherapy followed by alternating chemo-radiotherapy in stage IV undifferentiated nasopharyngeal carcinoma

In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patients with previously untreated T4 and/or N2–3 undifferentiated nasopharyngeal carcinoma were consecutively enrolled and initially treated with 3 courses of epidoxorubicin, 90 mg/m2, day 1 and cisplatin, 40 mg/m2, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/m2/day, days 1–4 and fluorouracil, 200 mg/m2/day, days 1–4, i.v. bolus, (weeks 1, 4, 7) alternated to 3 courses of radiation (week 2–3, 5–6, 8–9–10), with a single daily fractionation, up to 70 Gy. WHO histology was type 2 in 30% and type 3 in 70% of the patients. 57% had T4 and 77% N2–3 disease. All the patients are evaluable for toxicity and response. All but one received 3 courses of induction chemotherapy. Toxicity was mild to moderate in any case. At the end of the induction phase 10% of CRs, 83.3% of PRs and 6.7% of SD were recorded. All the patients but one had the planned number of chemotherapy courses in the alternating phase and all received the planned radiation dose. One patient out of 3 developed grade III–IV mucositis. Haematological toxicity was generally mild to moderate. At the final response evaluation 86.7% of CRs and 13.3% of PRs were observed. At a median follow-up of 31 months, 13.3% of patients had a loco-regional progression and 20% developed distant metastases. The 3-year actuarial progression-free survival and overall survival rates were 64% and 83%. Induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients' compliance optimal. This approach showed a very promising activity on locally advanced UNPC and merits to be investigated in phase III studies. © 2000 Cancer Research Campaign http://www.bjcancer.co

Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study

Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients

Syndecan-1 expression has prognostic significance in head and neck carcinoma

The syndecans are a family of cell-surface heparan sulphate proteoglycans that regulate cell behaviour by binding extracellular matrix molecules such as growth factors. The syndecan family has four members, of which syndecan-1 is the most studied and best characterized. We have studied the prognostic significance of syndecan-1 expression in squamous cell carcinoma (SCC) of the head and neck treated with surgery and post-operative radiotherapy. Paraffin-embedded tissue samples taken from 175 patients with primary SCC, followed up from 2 to 15 years after surgery, were studied for expression of syndecan-1 by immunohistochemistry. A low number (≤50%, the median value) of syndecan-1-positive tumour cells was associated with low histological grade of differentiation (P < 0.0001), a large primary tumour size (T1–2 vs T3–4, P = 0.02), positive nodal status (N0 vs N1–3, P = 0.0006), and high clinical stage (stage I or II vs III or IV, P < 0.0001). Low syndecan-1 expression was also associated with unfavourable overall survival in a univariate analysis (P = 0.001). In a multivariate survival analysis, the clinical stage and syndecan-1 expression were the only independent prognostic factors. We conclude that syndecan-1 is a novel prognostic factor in SCC of the head and neck treated with surgery and post-operative radiotherapy. © 1999 Cancer Research Campaig

State-of-the-art management of locally advanced head and neck cancer

During the past 20 years, treatments for head and neck squamous cell carcinoma (HNSCC) have changed dramatically owing largely to the advent of novel approaches such as combined modality therapy as well as improvements in surgical and radiotherapeutic techniques. Locally advanced disease in particular, which engendered very high recurrence and mortality rates, is now associated with long-term disease-free survival in the majority of cases. This article will focus on locally advanced HNSCC, which frequently remains a clinical challenge, review state-of-the-art therapy, and introduce promising novel therapies. The field continues to evolve rapidly with new evidence during the past year clearly establishing the benefit of adjuvant chemoradiotherapy (CRT), as well as early evidence showing improved survival with the use of an epidermal growth factor receptor inhibitor in combination with radiotherapy. There are varied regimens in use for patients with locally advanced disease, but at the same time the multitude of options can plague the clinician when trying to select the most appropriate one. This article will attempt to put the various approaches into perspective and propose an evidence-based treatment algorithm

Gli indicatori tra costruzione teorica e spendibilit\ue0 empirica: un caso di studio

Il saggio discute la relazione circolare e abduttiva che si viene a creare nel corso del processo di costruzione degli indicatori tra dimensione teorica e praticabilit\ue0 empirica e le specifiche connatazioni che tale processo assume quando dagli indicatori scelti nascono conseguenze pratiche importanti. Il saggio discute anche dell'importanza non solo della selezione degli indicatori, ma anche del tipo di elaborazioni statistiche cui sono sottoposti nel determinare i risultati finali e delle modalit\ue0 con le quali i decisori possono intervenire nel processo