SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare but locally aggressive malignancy of the nasal cavity and paranasal sinuses, representing about only 1 % of all head and neck malignancies. It is characterized by loss of INI-1 in the tumour cells under immunohistochemical staining. The overwhelming majority of INI-1 deficient sinonasal carcinoma presents very late at diagnosis, owing to its very similar clinical presentation to other benign conditions like allergic rhinitis, nasal polyps, chronic sinusitis, and some more common malignancies like human papilloma virus-associated squamous cell carcinoma, extranodal NK/T cells lymphoma, mucosal melanoma. Therefore, complete surgical removal remains very challenging and most of the time impossible.~Currently, aggressive multimodality treatment of INI-1-deficient sinonasal carcinomas is based on experience with other sinonasal malignancies including case series of sinonasal undifferentiated carcinoma. Upfront surgical resection for potentially resectable cases, followed by adjuvant radiation therapy or adjuvant chemoradiation. Also under investigation is the use of induction chemotherapy followed by surgery and adjuvant radiation in the treatment of sinonasal malignancy.~In view of the above, the investigators are now proposing a phase II single-arm study on tazemetostat in combination with TPF as preoperative therapy for locally advanced non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma, followed by radical resection and/or post-operative radiation therapy (with or without concurrent chemotherapy), and tazemetostat for another 6 months. It is hypothesized that addition of tazemetostat will improve objective response rate, resectability rate, orbit preservation rate, and hopefully survival outcomes with manageable safety profiles.
SMARCB1-deficient sinonasal carcinoma is very locally advanced malignancy at diagnosis which often precluded upfront radical resection. The investigators are now proposing a phase II single-arm study on tazemetostat in combination with docetaxel, cisplatin and 5-FU (known as TPF regimen) as preoperative therapy for locally advanced non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma, followed by radical resection and/or post-operative radiation therapy (with or without concurrent chemotherapy), and tazemetostat for another 6 months. It is hypothesized that addition of tazemetostat will improve objective response rate, resectability rate, orbit preservation rate after surgery, and hopefully survival outcomes with manageable safety profiles.