Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma

Abstract

Purpose: To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC).

Patients and methods: A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety.

Results: Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control.

Conclusion: Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.

Trial registration: ClinicalTrials.gov NCT01542931.

Fig 1.

CONSORT diagram.

Fig 2.

(A) Overall and (B) disease-free survival in the control and experimental arms. TPF, docetaxel, cisplatin, and fluorouracil.

Fig 3.

Subgroup analysis of (A) overall and disease-free survival and (B) locoregional recurrence–free and distant metastasis–free survival in the control and experimental arms. HR, hazard ratio; M/P, moderately/poorly.

Fig A1.

(A) Locoregional recurrence–free and (B) distant metastasis–free survival in the control and experimental arms. TPF, docetaxel, cisplatin, and fluorouracil.

Fig A2.

(A to D) Pathologic and (E to H) clinical response for (A, E) overall, (B, F) disease-free, (C, G) locoregional recurrence–free, and (D, H) distant metastasis–free survival. The landmark point was set at the time of response evaluation.