4244 - Concurrent chemoradiotherapy (CCRT) versus induction docetaxel, cisplatin and 5-fluorouracil (TPF) followed by CCRT in locally advanced hypopharyngeal and base of tongue cancer: A randomized phase II study

Background

To date, clinical trials have not consistently supported the use of induction chemotherapy (IC) for locally advanced head and neck squamous cell cancer (LASCC). Hypopharyngx and base of tongue (BOT) cancer has shown relatively poor survival compared to other LASCC. We tried to investigate the role of IC for improvement over current chemoradiotherapy (CRT) in patients with locally advanced hypopharynx and BOT cancer.

Methods

Treatment-naïve patients with nonmetastatic stage III/IV hypopharyngeal or BOT cancer were randomly assigned to receive CRT alone (CRT arm: cisplatin 100mg/m² 3-weekly for 2 times plus radiotherapy 68.4Gy/30fraction on weekday) versus two 21-day cycles of IC (docetaxel 75mg/m² on day 1, cisplatin 75mg/m² on day 1, and fluorouracil 750mg/m² on days 1 to 4) followed by same CRT regimen (IC arm). The primary endpoint was progression-free survival (PFS) and 90 patients are required to show the superiority of IC arm with one-sided alpha 0.1 and power of 0.85.

Results

This study closed early after enrollment of 36 patients (19 in CRT arm and 17 in IC arm) because of slow accrual. After a median follow up of 47.2 months, there was no significant difference in PFS: the median PFS were 26.8 months for CRT arm and not reached for IC arm (Hazard ratio: 0.55, 95% CI 0.19-1.60). However, the survival curves widely separated with a plateau after 3-years, suggesting the survival benefit from induction chemotherapy: 3-year PFS rates were 45% and 68%, and 3-year overall survival rates were 56% and 86% (HR: 0.35, 95% CI: 0.07-1.69), in CRT and IC arms, respectively. In both subgroups with BOT and hypopharyngeal cancer, survival outcomes of IC arm were also insignificantly superior to those of CRT arm. All adverse events were manageable and there was no grade 3/4 toxicity except one patient had Gr3 stomatitis in IC arm.

Conclusions

This study failed to demonstrate that induction TPF chemotherapy improves survival in patients with BOT and hypopharyngeal cancer, possibly due to small number of subjects. However, it suggested favorable outcome with induction chemotherapy, and further large randomized studies are needed to this population.

Clinical trial identification

NCT01312350

Legal entity responsible for the study

Samsung medical center

Funding

None

Disclosure

All authors have declared no conflicts of interest.