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.

Treatments for locally advanced oropharyngeal cancer: A systematic review of clinical effectiveness and cost-effectiveness.

“…While TLM or TORS is typically used to treat early stage disease, the results of our systematic review on the clinical effectiveness of transoral surgery in locally advanced oropharyngeal cancer agree with findings from two systematic reviews on all stages and on early 36 oropharyngeal cancer, which found comparable oncologic outcomes between TORS and IMRT, and agreed with a systematic review on all stages of oropharyngeal cancer that found TLM or TORS may offer the potential to improve swallowing outcomes compared with CRT.…”

Presurgical induction chemotherapy for squamous cell carcinoma of the tonsil

“…There have been trials of induction chemotherapy followed by concurrent chemoradiotherapy for tumors of the head and neck. Several phase II/III trials using cisplatin/docetaxel/5‐FU (TPF) induction triple therapy for oral cavity cancers inclusive of the tonsil have recently been published, showing mixed results . The overwhelming cause for the failures of these trials is the toxicities associated with induction regimens.…”

Clinicopathological and prognostic significance of cyclooxygenase-2 expression in head and neck cancer: A meta-analysis

“…These results hinted that COX-2 expression could work as a prognostic factor for patients with HNC. Radiotherapy and platinum-based chemotherapy are important treatment options for HNC [65, 66]. Several reports have revealed that COX-2 relates with radiosensitivity and platinum resistance of HNC [67, 68], which testifies the prognostic role of COX-2 on the other side.…”