Multidisciplinary approach in advanced cancer of the oral cavity: Outcome with neoadjuvant chemotherapy according to intention-to-treat local therapy. A Phase II Study

Objectives: To determine outcomes in local-regional control and overall survival in patients with squamous locally advanced cancer of the oral cavity, based on intention-to-treat with neoadjuvant chemotherapy followed by surgery or radiation therapy. Methods: Two hundred and four out of 1,089 patients analyzed met the defined criteria. All had squamous cell carcinomas of the oral cavity in stage III or in nonmetastatic stage IV and were selected for surgery or radiation therapy (if located in the tonsils or in the base of the tongue). Chemotherapy was based on cisplatin 120 mg/m² i.v. day 1 plus bleomycin 20 mg/m² days 1-5 in continuous i.v. perfusion or plus 5-fluorouracil 1,000 mg/m² days 1-5 in continuous i.v. perfusion. A total of 418 cycles were given to 204 patients (mean 2.049 per patient). Definitive surgery (n = 73; plus adjuvant radiation therapy) or definitive radiation therapy (n = 131) was performed. Results: One hundred thirty-five out of 204 (66%) patients were chemotherapy responders, 16% complete and 50% partial. One hundred ninety-four patients (95%) completed 2 courses of chemotherapy. After neoadjuvant chemotherapy, 34 out of 46 patients considered inoperable initially (74%) obtained a disease-free status with surgery. Eighty-three percent of surgical patients obtained a disease-free status (initial tumor control) versus 72% of radiation therapy patients. Disease-free survival rates at 5 years were 26 and 22%, respectively. A better prognosis was observed in stage III over IV (p = 0.02); primary tumor in the retromolar trigone, palate or buccal mucosa over tongue, tonsil or floor of the mouth (p = 0.0085); negative cervical nodes over positive (p = 0.0186); responders to chemotherapy over nonresponders (p = 0.0003); and adjuvant postsurgical radiation therapy (p = 0.0013). Causes of death were relapses in local area (86%), regional nodes (10.5%) or distant metastases (3.5%). Eleven patients (5%) died of a second primary. The main toxic effects were vomiting in 9% of patients and hemolytic-uremic syndrome in 3% of the patients treated with bleomycin. Conclusions: In locally advanced squamous cell carcinoma of the oral cavity, neoadjuvant chemotherapy induces a high response rate that may facilitate definitive surgery or radiotherapy. In this study, patients have an acceptable long-term survival.