Adding a third drug (docetaxel) to a standard two-drug initial chemotherapy regimen significantly improves the long-term survival of patients with head and neck cancer, reducing the likelihood of dying by 26% over 6 years. The long-term results of the TAX 324 trial published Online First in The Lancet Oncology, confirm that this three-drug regimen should become the standard of care for patients who are suitable for induction therapy.
Every year, cancers of the head and neck are diagnosed in more than 40 000 people in the USA. Standard treatment for these patients involves combining radiotherapy and chemotherapy with or without surgery, and the addition of induction chemotherapy has been shown to prolong survival. However, the best ways of combining these treatments remains unclear.
In recent years, cisplatin plus fluorouracil (PF) has become a standard induction chemotherapy combination and has been shown to significantly prolong survival.
The TAX 324 trial was designed to establish whether the addition of docetaxel to initial chemotherapy with cisplatin and fluorouracil (PF) might help patients with locally advanced head and neck cancer live longer. Between May 1999 and December 2003, 501 patients were recruited from 55 centres across the USA, Canada, Argentina, and Europe.
In 2007, initial results (minimum follow-up 2 years) showed that induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) significantly improved survival compared with PF.
To establish the durability of this survival benefit, Jochen Lorch from the Dana-Farber Cancer Institute, Boston, USA and colleagues evaluated the long-term follow-up of patients from the TAX 324 trial.
Over 6 years, the survival advantage was sustained and the addition of docetaxel reduced the risk of death by 26%.
Overall survival was significantly better in the TPF group (70.6 months) than in the PF group (34.8 months). Survival at 5 years was 52% in the three-drug combination group and 42% in the two-drug group.
Additionally, progression-free survival was significantly longer for patients receiving the TPF than those on PF (median 38.1 months vs 13.2 months).
Further analyses showed that patients with hypopharyngeal and laryngeal cancers had significantly prolonged PFS from treatment with the three-drug regimen compared with the two-drug regimen, and oropharyngeal cancers treated with TPF showed an overall survival benefit.
Long-term toxic effects (measured by the use of tracheostomy and dependence on gastric feeding tubes) did not differ between the treatment groups.
The authors say: "The updated results of our study suggest that the survival benefit of sequential therapy with TPF continues well beyond the 2 years of the original analysis and was sustained at the same level."
They conclude: "Patients who are candidates for induction chemotherapy should be treated with TPF."
In a Comment, June Corry and Danny Rischin from the Peter MacCallum Cancer Centre, Melbourne, Australia, say that the role of induction chemotherapy in advanced head and neck cancer is still unclear: "Use of TPF requires a subsequent compromise in dose intensity of the chemotherapy that can be given concomitantly with radiation…[as such] there are concerns that subjecting patients to a protracted course of treatment might compromise the delivery of the concomitant component, which has been shown to have the largest effect on locoregional control and overall survival."
They add: "Hopefully, other completed or ongoing trials will provide the answers we need to determine whether there is a role for TPF-induction chemotherapy."
Dr Jochen Lorch, Dana-Farber Cancer Institute, Boston, USA. T) +1 617 632 3090 E) jochen_lorch@dfci.harvard.edu
Professor June Corry, Peter MacCallum Cancer Centre, Melbourne, Australia. T) +61 3 96561648 E) june.corry@petermac.org
Journal
The Lancet Oncology