Neoadjuvant Chemotherapy and Surgery versus Surgery for Organ Preservation of T3 and T4a Nasal and Paranasal Sinus Sq...

PURPOSE: Neoadjuvant chemotherapy for structure preservation (SP) in nasal and paranasal sinus squamous cell carcinoma (NPNSCC) has been described in single-institution studies but not in randomized studies. EA3163 was a randomized study investigating whether cytoreductive neoadjuvant chemotherapy would improve SP or overall survival (OS). PATIENTS AND METHODS: Patients with T3/T4a and select T4b NPNSCC requiring orbital or base of skull (BOS) resection were randomized to surgery (arm A) versus surgery preceded by docetaxel/cisplatin for three cycles (arm B). The degree of anticipated SP (orbit and BOS) was required preoperatively and after chemotherapy. SP was noted at surgery. Co-primary objectives were the SP rate (orbit/BOS) and OS. Eighty-two patients needed to be accrued for 81% power with a 0.1 one-sided alpha using Fisher's exact test for SP rate and 83% with a 0.1 one-sided alpha using the log-rank test for OS. RESULTS: Among 23 evaluable patients, the overall SP rate was 30%: 15% in arm A (N = 2/13; 95% confidence interval (CI), 1.9%-45.4%) and 50% in arm B (N = 5/10; 95% CI, 18.7%-81.3%; P = 0.17). Among 18 patients with pathologic T3/T4a disease, the overall SP rate was 39%: 18% in arm A (N = 2/11; 95% CI, 2.3%-51.8%) and 71% in arm B (N = 5/7; 95% CI, 29.0%-96.3%; P = 0.049). Orbit and BOS-specific preservation rates were 38% (95% CI, 8.5%-75.5%) versus 83% (95% CI, 35.9%-99.6%) and 33% (95% CI, 9.9%-65.1%) versus 67% (95% CI, 29.9%-92.5%) in arm A versus B, respectively. The most common grade ≥3 toxicities included mucositis, anemia, nausea and lymphopenia (all >10%). No grade 5 events were reported. CONCLUSIONS: These results support neoadjuvant chemotherapy as an effective intervention for SP in T3/T4a NPNSCC and deserve further evaluation.