Platinum Based Chemotherapy With Radiation Sinonasal

Treatment Guidelines and Outcome

Surgery with platinum-based postoperative chemotherapy should be considered the treatment of choice for sinonasal neuroendocrine carcinomas with limited local extent (Perez-Ordonez et al. 1998). According to Galera-Ruiz et al. (2001b), advanced lesions are best treated by a regimen similar to that of small cell lung cancer, which includes a combination of chemotherapy (cisplatin + etopo-side) and radiotherapy. Differently, in the experience of Memorial Sloan Kettering Cancer Center, a good response was obtained with platinum-based neoad-juvant chemotherapy and radiotherapy followed by surgery (Perez-Ordonez et al. 1998). A similar combination of chemotherapy, radiotherapy, and possibly subsequent surgery has been proposed by Fitzek et al. (2002). In case of disseminated disease, platinum-based chemotherapy is the treatment of choice. Radiotherapy may also have a role in the palliation of non resectable lesions.

Even though local recurrence is the most common cause of treatment failure, regional and distant spreading (especially to the brain and spine) may also occur (Smith et al. 2000). In the series from Perez-Ordonez et al. (1998), after a 37-month follow up, only one patient (16.7%) affected by sinonasal neuroendocrine carcinoma was free of disease, one (16.7%) died for local recurrence and distant metastases, and the remaining four (66.6%) were alive with disease (local and/or distant recurrence).

Due to the aggressiveness of sinonasal undif-ferentiated carcinoma and to its high probability of systemic spreading, almost all authors concur on the need of a treatment which should include a combination of radiotherapy and chemotherapy. By contrast, the role of surgery is controversial.

Some authors (Gorelick et al. 2000; Musy et al. 2002; Kim et al. 2004) have proposed an integrated therapeutic protocol which included surgery. The choice of this therapeutic protocol is supported by either the detection in the majority of patients of viable neoplastic cells within the field of irradiation (Musy et al. 2002) and by the observation of a better survival when surgery was added to chemotherapy with radiation (Kim et al. 2004). In the paper by Musy et al. (2002), the overall 2-year survival for patients affected by sinonasal undifferentiated carcinoma was 47%; when stratified by treatment modality, survival was as high as 64% for patients who underwent cra-niofacial resection and 25% for those who did not. However, some bias related to treatment selection in relation to the stage of the lesion might have influenced the results. More recently, Rischin et al. (2004) reported promising results in the treatment of locally advanced sinonasal undifferentiated carcinoma with a regimen of neoadjuvant chemotherapy (5-fluoro-

uracil and platinum) followed by concurrent chemo-radiation. With this protocol, they achieved a 2-year disease-free and overall survival of 43% and 64%, respectively. Surgery should be reserved only for those patients with residual resectable disease.

Local-regional and distant metastases develop in a high rate of patients (63% and 50%, respectively), prevalently within two years from treatment (Kim et al. 2004).

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