Induction chemotherapy for head and neck cancer: will history repeat itself?

Locally advanced squamous cell head and neck cancer remains a therapeutic challenge for multidisciplinary teams. Despite high objective response rates, induction chemotherapy has not resulted in tangible benefit in multiple randomized trials. In recent years, as most evidence solidified the role of concurrent chemotherapy and radiation as either primary or postoperative therapy for locally advanced head and neck cancer, induction chemotherapy fell out of scope and practice. The failure of older randomized trials to show a survival benefit from induction chemotherapy can be attributed to several factors. It is possible that the predominance of locoregional failure did not allow any added benefit from better systemic control to translate into a survival advantage. Alternatively, seemingly active chemotherapy regimens may have been suboptimal. Nevertheless, recent developments have altered our perception of head and neck cancer and its treatment. Locoregional control has dramatically improved with concurrent chemoradiotherapy. Of note is that none of the previously conducted randomized trials of induction chemotherapy used concurrent chemoradiotherapy in the control arm. Moreover, we witnessed the development of better combination regimens that improved efficacy in the induction setting. The previously standard cisplatin/5-fluoruracil (5-FU) combination is being replaced by the triple combination of taxane/ cisplatin/5-FU. Randomized trials showed that increased activity with the triplet regimen resulted in improved long-term disease control and survival. Finally, cetuximab, an active epidermal growth factor receptor inhibitor, is entering clinical practice and is expected to change the standard of therapy. With the emergence of more efficacious systemic therapies, the role of induction therapy warrants reevaluation. A number of randomized trials are planned or currently ongoing to investigate concurrent chemoradiotherapy with or without induction. These trials are anticipated to redefine the role of induction chemotherapy for head and neck cancer.