Purpose: Prognosis of patients with advanced oral cavity cancer is worth improving. Chemotherapy has been reported to be especially active in oral cavity tumors. Here we repeat the results of a randomized, multicenter trial enrolling patients with a resectable, stage T2–T4 (> 3 cm), N0–N2, M0 untreated, squamous cell carcinoma of the oral cavity. Patients and Methods: Patients were randomly assigned to three cycles of cisplatin and fluorouracil followed by surgery (chemotherapy arm) or surgery alone (control arm). In both arms, postoperative radiotherapy was reserved to high-risk patients, and surgery was modulated depending on the tumor’s closeness to the mandible. Patients’ accrual was opened in 1989 and closed in 1999. It included 195 patients. Results: In the chemotherapy arm, three toxic deaths were recorded. No significant difference in overall survival was found. Five-year overall survival was, for both arms, 55%. Postoperative radiotherapy was administered in 33% of patients in the chemotherapy arm, versus 46% in the control arm. A mandible resection was performed in 52% of patients in the control arm, versus 31% in the chemotherapy arm. Conclusion: The addition of primary chemotherapy to standard surgery was unable to improve survival. However, in this study, primary chemotherapy seemed to play a role in reducing the number of patients who needed to undergo mandibulectomy and/or radiation therapy. Variations in the criteria used to select patients for these treatment options may make it difficult to generalize these results, but there appears to be room for using preoperative chemotherapy to spare demolitive surgery and/or radiation therapy in patients with advanced, resectable oral cavity cancer.

Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting. We present the long-term results of a randomized trial of induction chemotherapy in resectable oral cavity cancer. A randomized, parallel, multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m² and fluorouracil 1000 mg/m² (120-h infusion administered every 21 days) in stage T2–T4, N0–N2, previously untreated patients with advanced disease. Control group received upfront surgery. Postoperative radiation was offered to both arms when pathologic risk features were identified. The co-primary end points were the occurrence of locoregional or distant tumour relapse, and death. Among the 198 enrolled patients, with a median follow-up of 11.5 years, there was no difference in the incidence of locoregional relapse between chemotherapy and control group (P = 0.6337), nor in distant metastasis development (P = 0.1527). There was also no difference between groups in overall survival (P = 0.3402). Patients with a pathological complete response (pCR) had higher probability of survival than those without (10-year OS: 76.2% versus 41.3%, P = 0.0004). Late toxicities in patients with a minimum follow-up of 60 months (42 in each group) were similar between arms, except from fibrosis (cumulative incidence 40% versus 22% in chemotherapy arm) and grade 2 dysphagia (14% versus 5%). Long-term follow-up of this randomized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer. Late toxicity was similar in the two arms except for fibrosis and dysphagia, which were less in the chemotherapy arm. The survival benefit for patients achieving a pCR was maintained.