Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma

Abstract

Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC.

Keywords: 5-fluorouracil; cisplatin; docetaxel; induction chemotherapy; oral squamous cell carcinoma.

Figure 1. CONSORT diagram

Figure 2

Comparison of A. overall survival, B. disease-free survival, C. locoregional recurrence-free survival, and D. distant metastasis-free survival in the experimental and control groups.

Figure 3. Comparison of overall survival, disease-free survival, locoregional recurrence-free survival and distant metastasis-free survival between the patients with favorable and unfavorable pathologic responses (upper panel), between favorable pathologic responses and the control group (middle panel), and between unfavorable pathologic responses and the control group (lower panel)

Figure 4. Subgroup analysis of overall survival, disease-free survival, locoregional recurrence-free survival and distant metastasis-free survival between the experimental and control groups