Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions

Abstract

Background: The value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet cisplatin and fluorouracil. We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.

Design: We nonsystematically reviewed published phase III clinical trials on TPF ICT in a variety of LA SCCHN patient populations conducted between 1990 and 2017.

Results: TPF may confer survival and organ preservation benefits in a subgroup of patients with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients with operable disease or good prognosis (who are not candidates for organ preservation) may benefit from TPF induction in terms of reducing local and distant failure rates and facilitating treatment deintensification in selected populations. The safe administration of TPF requires treatment by a multidisciplinary team at an experienced institution. The management of adverse events associated with TPF and post-ICT radiotherapy-based treatment is crucial. Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with radiotherapy (i.e. cetuximab or carboplatin plus radiotherapy) appear promising and must be investigated further.

Conclusions: TPF is an evidence-based ICT regimen of choice in LA SCCHN and confers benefits in suitable patients when it is administered safely by an experienced multidisciplinary team and paired with the optimal post-ICT regimen, for which, however, no consensus currently exists.

Figure 1.

Current standard-of-care paradigm in LA SCCHN. *ICT→RT is only an accepted standard approach for larynx preservation in locoregionally advanced larynx and hypopharynx cancer. ICT, induction chemotherapy; LA SCCHN, locally advanced squamous cell carcinoma of the head and neck.

Figure 2.

TPF versus PF in two different patient cohorts (TAX 323/EORC 24971 and TAX 324). 5-FU, fluorouracil; HR, hazard ratio; mOS, median overall survival; PF, cisplatin plus 5-FU; RT, radiotherapy; TPF, docetaxel, cisplatin, and 5-FU. From Refs [4, 5]. Copyright © 2007 Massachusetts Medical Society. Reprinted with permission.