A growing body of data from randomized clinical trials has demonstrated that induction chemotherapy — in combination with chemoradiotherapy — may play an important role in the treatment localized head and neck cancers.
The standard neoadjuvant chemotherapy regimen has consisted of a platinum agent and 5-fluorouracil (5-FU), a regimen known as PF. More recently, the addition of a taxane such as docetaxel (or, less commonly, paclitaxel) to the PF regimen (a triple combination known as TPF) is emerging as a more effective and less toxic standard for induction chemotherapy.
Two large, randomized trials — the Veterans Affairs Laryngeal Cancer Study Group trialand a phase 3 trial conducted by the European Organization for Research and Treatment of Cancer (EORTC) — have demonstrated the benefit of induction chemotherapy with PF (100 mg/m2 of cisplatin on day 1 and 1000 mg/m2 of 5-FU by continuous infusion on days 1-5) with respect to organ preservation. In these trials, overall survival rates were similar in patients receiving either induction PF chemotherapy and radiation or surgery and radiation therapy. In patients with more advanced unresectable tumors, PF induction therapy has been shown to produce long-term survival benefits with overall survival times in a subset of inoperable patients receiving chemotherapy of 21% at 5 years and 16% at 10 years compared with 8% and 6%, respectively, in patients not receiving chemotherapy. In a phase 3 trial of neoadjuvant chemotherapy in patients with oropharyngeal cancer conducted by the French Groupe d’Etude des Tumeurs de la Tete et du Cou (GETTEC), the median overall survival time for patients with both resectable and unresectable tumors was 5.1 years when PF induction chemotherapy was followed by locoregional therapy vs 3.3 years for those who did not receive PF induction chemotherapy (P = .03).
A number of randomized trial have demonstrated improved organ preservation or survival with TPF compared with PF. The phase 3 TAX 323 trial, a direct comparison of PF and TPF induction chemotherapy conducted by the EORTC, included patients with locally advanced and unresectable squamous cell head and neck cancer who were randomized to receive induction therapy with either PF or TPF every 3 weeks for 4 cycles, followed by radiotherapy or surgery.
The international TAX 324 trial assessed PF induction chemotherapy, with or without docetaxel, followed by chemoradiotherapy and surgical resection in patients with locally advanced head and neck cancer. Finally, a randomized phase 3 trial comparing PF induction chemotherapy with and without docetaxel in patients with laryngeal cancer demonstrated an improvement in organ preservation with the addition of the taxane to the PF regimen.
Although the question is still being studied in the DeCIDE trial — Docetaxel Based emotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer — a phase 3 trial sponsored by the University of Chicago, NCCN already lists induction chemotherapy as an option.Two European randomized trials comparing a sequential treatment approach including TPF induction chemotherapy and chemoradiotherapy vs standard chemoradiotherapy alone for the treatment of head and neck cancer are in progress, and data are anticipated within 2 years.
The US Food and Drug Administration (FDA) has approved Taxotere Injection Concentrate combined with cisplatin and 5-fluorouracil for induction therapy of locally advance squamous cell carcinoma of the head and neck before chemoradiotherapy and surgery.
NCCN.ORG, Head and Neck 2012
Salama JK, Haddad RI, Kies MS, Busse PM, Dong L, Brizel DM, Eisbruch A, Tishler RB, Trotti AM, Garden AS.
Clinical practice guidance for radiotherapy planning after induction chemotherapy in locoregionally advanced head-and-neck cancer.Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):725-33.
It’s Posner MR, Haddad RI, Wirth L, et al. Induction chemotherapy in locally advanced squamous cell cancer of the head and neck: evolution of the sequential treatment approach. Semin Oncol. 2004;31:778-785.
Remenar E, Van Herpen C, Germa Lluch J, et al. A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971. Proc Am Soc Clin Oncol. 2006;24:284s. Abstract 5516.
Zorat PL, Paccagnella A, Cavaniglia G, et al. Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up. J Natl Cancer Inst. 2004;96:1714-1717.
Posner MR, Haddad RI, Wirth LJ. The evolution of induction chemotherapy and sequential therapy for locally advanced squamous cell cancer of the head and neck. American Society of Clinical Oncology Educational Book, 2006; pp 346-352.
Calais G, Pointreau Y, Alfonsi M, et al. Randomized phase III trial comparing induction chemotherapy using cisplatin (P) fluorouracil (F) with or without docetaxel (T) for organ preservation in hypopharynx and larynx cancer. Preliminary results of GORTEC 2000-01. Proc Am Soc Clin Oncol. 2006;24:281s.