Neoadjuvant Chemotherapy of Three Cycles or More Improve Survival of Patients with N2-3 Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is the most common cancer originating from the epithelial cells that cover the surface of nasopharynx. It is a rare malignancy with an average incidence under 1 per 100,000 person-years except certain regions of East Asia and Africa, where the incidence may reach 80 per 100,000 personyears. Due to anatomical complexity of NPC and its tendency to metastasize,radiotherapy instead of surgery is the mainstay of treatment. Since advent of intensity-modulated radiation therapys (IMRT) and concurrent chemotherapy (CCT), the 5-year overall survival of NPC has reached 83.0% now. Unfortunately, distant metastases remain the major causes of failure. More than 30% of patients with advanced loco-regional disease eventually died of distant failure. 

Although meta-analysis showed neoadjuvant chemotherapy (NACT) could significantly reduce distant failures in head and neck squamous cell carcinoma and improve prognosis [7]. The roles of NACT in NPC remain uncertain though a series of phase II clinical trials have recently indicated that patients with 2-3 cycles of NACT before concurrent chemo-radiation had a trend of better survival than those without NACT. It is known that the metastasis risk of NPC correlates with both T and N stage, but N stage is by far the most significant predicting factor. Even after multimodality treatment based on IMRT plus CCT, stage N2-3 disease was proved to be an independent factor predicting a greater risk of distant failure and poor overall survival (5-year distant-metastasis rate, 35.2%). Clinical outcome of these patients might be further improved through eradicating metastases. However, the previous studies on NACT of NPC almost enrolled patients with Stage III-IVB diseases. There was no published study focusing on N2-3 NPC patients, or appropriate cycle number of NACT for them. Therefore, we performed a casecontrol pilot study to evaluate the impact of NACT of different cycles on survival of patients with N2-3 NPC.

Patients with pathologically diagnosed and previously untreated NPC in our hospital from January 1st 2008 to December 31st 2009 were initially considered. The ones would be included if they had age younger than 70 years old and T1-4N2-3M0 NPC. Stage of all patients was determined through magnetic resonance imaging of head and neck (HN-MRI), whole-body bone scan and thoraco-abdominal computed tomography (or chest radiograph plus abdominal ultrasonography) and according to the Union Internationale Contre le Cancer/American Joint Cancer Committee TNM classification version 2002. After staging, 593 consecutive patients with N2-3 disease were enrolled into our study.

The exclusion criteria included: (i) Karnofsky performance score <80; (ii)severe dysfunction of heart, lung, liver or kidney; (iii) history of other malignancies; (iv) prior chemotherapy or radiotherapy; (v) distant metastases before or during radiotherapy. 40 patients were excluded for distant metastases before or during radiotherapy. Then a total of 553 patients with N2-3 non-metastatic NPC were eligible for this study. Among these patients, 102 cases received NACT of 3 cycles or more (NACT≥3 group) and were defined as the experimental group. 185 did not receive NACT (NACT=0 group) and 266 received NACT of 2 cycles (NACT=2 group). Through the frequency-matching technique, patients of the NACT≥3 group were then matched in a ratio of 1:2:1 to those of the NACT=2 group and the NACT=0 group, which were defined as the control groups. Patients were matched when they had the same histological subtype (squamous cell carcinoma vs. non-keratinizing carcinoma vs. undifferentiated carcinoma), the same N stage (N2 vs. N3), the same NACT regimen (docetaxel plus cisplatin vs. cisplatin plus 5-fluorouracil) and the closet age. If there were several cases fit for matching to the same patient, selection was made randomly.