Induction Chemotherapy for Locoregionally Advanced Head and Neck Cancer: Past, Present, Future?

Abstract

The treatment of patients with locoregionally advanced squamous cell cancer of the head and neck is still evolving. Induction chemotherapy (IC) is widely used in this patient population and it is unclear how to best incorporate IC into multimodality treatment. Recently, the results of two randomized clinical trials were presented (the PARADIGM and Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer trials), which showed no demonstrable benefit of IC followed by concurrent chemoradiation over concurrent chemoradiotherapy alone. However, a lower rate of distant metastatic disease was noted, suggesting that patients who are at high risk for metastatic disease may benefit from IC. This review summarizes how IC has evolved over the years, provides an update of recent developments, and discusses how IC may develop in the future. The Oncologist 2013;18:288 -293 Implications for Practice: Chemotherapy remains an integral part of management of the patient with locoregionally advanced squamous cell cancer of the head and neck. Data from recent trials do not show a survival advantage from induction chemotherapy (IC) over concurrent chemoradiation, but there are significant limitations to these studies as detailed in this review. IC remains an option for treating locoregionally advanced disease and could be considered for patients who are at high risk for distant failure. PERSPECTIVEMalignancies of the head and neck account for an estimated 52,160 newly diagnosed cancers in the U.S. each year, and nearly 12,000 deaths [1]. Squamous cell carcinoma of the head and neck (SCCHN) accounts for 90% of such malignancies. Despite treatment advances and early multimodality therapy, 5-year survival rates have remained dismal for patients with locoregionally advanced disease [2][3][4].Treatment strategies for patients with locoregionally advanced SCCHN have moved away from poorly effective singlemodality therapy and now encompass a multimodality approach (surgery, chemotherapy, radiation [RT], and targeted molecular therapeutics). In 2009, a large meta-analysis of the use of chemotherapy in head and neck cancer was updated, incorporating data from 87 trials and 17,346 patients, confirming the benefit of chemotherapy (given as concurrent chemoradiotherapy [CRT], induction chemotherapy [IC], or adjuvant treatment) in patients with locoregionally advanced SCCHN at all tumor sites (Table 1) [5,6]. The observed benefit of chemotherapy was an absolute 4.5% higher 5-year survival rate. Subgroup analysis revealed that there was a 2.4% overall survival (OS) benefit in favor of IC (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.90 -1.02; p ϭ .18) compared with locoregional treatment with concomitant CRT, with 26 of the 31 induction trials combining 5-fluorouracil (5-FU) and platinum therapy. Although the risk for death was lower in patients who were treated with concomitant CRT (HR, 0.81; 95% CI, 0.78 -0.86) in the indirect comparison, there was a more pronounced effec...

Clinical outcomes and toxicity after exclusive versus postoperative radiotherapy in supraglottic cancer: new solutions for old problems? The case of stage III and IV disease

“…Recently, the results of two randomized clinical trials have been presented (PARADIGM [22] and De-CIDE [23]); induction chemotherapy followed by concurrent chemo-radiation failed to demonstrate a local control benefit over concurrent chemo-radiotherapy alone. However, a lower rate of distant metastatic disease was noted, suggesting that patients who are at high risk for metastatic disease might benefit from induction chemotherapy [24]. The introduction of aggressive high-dose radio-chemotherapy improved disease control at expense of higher rates of treatment-induced toxicity.…”

Parameters of Stromal Activation and Epithelial to Mesenchymal Transition as Predictive Biomarkers for Induction Chemotherapy in Patients With Locally Advanced Oral Cavity and Oropharyngeal Squamous Cell Cancer

“…The addition of taxanes to the cisplatin and 5-fluorouracil induction regimen (TPF) has significantly improved outcomes in comparison with cisplatin and 5-fluorouracil (PF) alone [2,3]. However, as a recent phase II trial (DeCIDE) and a phase III trial (PARADIGM) may have been underpowered to show a survival advantage for TPF induction followed by chemoradiotherapy versus chemoradiotherapy alone [4,5], there is an ongoing debate which subset of patients may benefit from TPF [6,7]. Recently, it has been shown that growth differentiation factor 15 (GDF15) expression can be used as a prognostic biomarker for oral squamous cell carcinoma, and as a predictive biomarker for benefitting from TPF IC [8].…”

“…However, a lower rate of distant metastatic disease was noted in the above mentioned DeCIDE study, suggesting that patients who are at high risk for metastatic disease may benefit from IC [7]. For epithelial malignancies, the epithelial-mesenchymal transition (EMT) is considered to be the crucial event in the metastatic process [11].…”

Expresión de ciclo-oxigenasa 2 en carcinoma de laringe

“…Su tratamiento puede incluir cirugía, radioterapia y quimioterapia en distintas combinaciones. A pesar del avance en técnicas de tratamiento la sobrevida en estadios avanzados no se ha modificado significativamente en los últimos 20 años 2 . La comprensión de los fenómenos celulares que determinan la aparición de estos tumores podría ser la oportunidad de desarrollar nuevas estrategias terapéuticas.…”