Optimal treatment for recurrent/metastatic head and neck cancer

Abstract

While a large proportion of patients presenting with stage I and II squamous cell carcinoma of the head and neck (SCCHN) will remain disease free after single modality treatment, the majority of patients presenting in a more advanced disease stage and very often treated with a form of combined modality treatment, will eventually relapse, either locoregionally only, at distant sites only or both. A few patients with a locoregional recurrence can be salvaged by surgery or reirradiation. However, most patients with recurrent or metastatic (R/M) disease only qualify for palliative treatment. Treatment options in these patients include supportive care only, or in addition single agent chemotherapy, combination chemotherapy or targeted therapies either alone or in combination with cytotoxic agents. Prognostic factors analysis in such patients treated with (platinum-based) chemotherapy has identified five adverse prognostic factors, which seems worthwhile to take into consideration when performing trials; one pathologic feature (tumor cell differentiation) and four clinical baseline characteristics (ECOG performance status, weight loss, location of the primary tumor and prior radiotherapy). Moreover, it has been shown that response to systemic therapy has a major impact on survival. None of the trials performed in the past, even those with a reasonable sample size, have shown that aggressive platinum-based combination chemotherapy leads to survival benefit when compared to single agent methotrexate, cisplatin or 5-fluorouracil. After decades without real progress, a recent European randomized trial showed that adding cetuximab, the first clinically available EGFR-directed monoclonal antibody, to a standard chemotherapy regimen (platinum/5-fluorouracil) leads to an important survival benefit and this, with support of an additional smaller study in the US, has changed practice.

A genetic view of laryngeal cancer heterogeneity

“…Treatment options for metastatic disease include supportive care, single agent or a chemotherapy combination with or without targeted agents. 94 Pronostic factors of long-term survivors in metastatic SCCHN patients treated with pratinum-based chemotherapy were identified in the E1395 and E1393 randomized trials of the Eastern Cooperative Oncology Group (ECOG) and include: tumor cell differentiation, ECOG performance status (PS), weight loss, location of the primary tumor and prior radiotherapy. 95 The EXTREME trial showed that the combination of platinum-5Fluorouracil and cetuximab as first-line treatment in SSCHN improved OS, PFS and response rate with no decreased quality of life compared to the same schedule without the monoclonal antibody.…”

“…Classical drugs as methotrexate, cisplatin, 5-fluorouracil (5-FU) and bleomyin have shown responses of short duration (3-5 months) and 15-30% tumor reduction. 94 Of the more recent agents, taxanes (docetaxel and paclitaxel) improved response rates up to 43% in platinum resistant patients. 99 Furthermore, Afatinib is an irreversible ERBB family blocker with significant results in the second-line setting.…”

Role of Cetuximab in Pharyngocutaneous Fistula Closure due To Peristomal Recurrence

“…However, multimodality approaches are not often enough. Locoregional recurrence or distant methastasis (R/M-HNSCC) develop in significant number of the patients [1,3,8].…”

“…Overexpression of EGFR is related to poor prognostic factor in HNSCC [3,10]. Recently, this situation is used in the treatment as EGFR targeting strategies for HNSCC; monoclonal antibodies and tyrosine kinase inhibitors [1,10,11]. The best studied monoclonal antibody for HNSCC is cetuximab.…”

“…Cetuximab is a human-murine chimeric immunglobulin G1 monoclonal antibody which competitively binds to extracellular domain of the epidermal growth factor receptor (EGFR) [1]. It has a survival advantage in the treatment of patients with locoregionally advanced and platinum-refractory metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) [2].…”