Abstract
BackgroundCombined radiotherapy and chemotherapy is considered the standard of care for locally advanced nasopharyngeal carcinoma (LA-NPC) in Epstein-Barr virus infection endemic area. This study compared the long-term outcomes between LA-NPC patients treated with neoadjuvant chemotherapy followed by radiotherapy (NACT) and those treated with concurrent chemoradiotherapy (CCRT).MethodsFrom 2003 to 2007, a total of 128 histopathologically proven LA-NPC patients receiving either NACT or CCRT were consecutively enrolled at the National Cheng Kung University Hospital in Taiwan. NACT consisted of 3-week cycles of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL) or weekly alternated cisplatin on day 1 and fluorouracil and leucovorin on day 8 (P-FL). CCRT comprised 3-week cycles of cisplatin (Cis 100) or 4-week cycles of cisplatin and fluorouracil (PF4). The first failure site, disease free survival (DFS), overall survival (OS), and other prognostic factors were analyzed.ResultsThirty-eight patients (30%) received NACT. Median follow-up duration was 53 months. More patients with advanced nodal disease (N2-N3) (86.8% vs 67.8%, p =0.029) and advanced clinical stage (stage IVA-IVB) enrolled in the NACT group (55.2% vs 26.7%, p =0.002). For NACT, both MEPFL and P-FL had similar 5-year DFS and OS (52.9% vs 50%, p =0.860 and 73.5% vs 62.5%, p =0.342, respectively). For CCRT, both PF4 and Cis 100 had similar 5-year DFS and OS (62.8% vs 69.6%, p =0.49 and 72.9% vs 73.9%, p =0.72, respectively). Compared to CCRT, NACT had similar 5-year DFS and OS (51.5% vs 65.1%, p =0.28 and 71.7% vs 74.3%, p =0.91, respectively). Among patients who were recurrence-free in the first 2 years after treatment, those treated with NACT experienced poorer locoregional control compared to those treated with CCRT (Hazard ratio =2.57, 95% confidence interval: 1.02 to 6.47, p =0.046).ConclusionsFor LA-NPC, both CCRT and NACT were similarly efficacious treatment strategies in terms of long-term disease control and survival probability. Close locoregional follow-up is recommended for patients receiving NACT, because these patients are more prone to develop locoregional failure than patients receiving CCRT.
Highlights
Combined radiotherapy and chemotherapy is considered the standard of care for locally advanced nasopharyngeal carcinoma (LA-Nasopharyngeal carcinoma (NPC)) in Epstein-Barr virus infection endemic area
Zhang et al reported that the relative benefit of this approach might be less in NPC-endemic area than that in non-NPC-endemic area [8] and Lee et al reported after median follow-up 5.9 years, the administration of cisplatin plus adjuvant cisplatin-fluorouracil concurrent with radiotherapy showed a better 5-year progression free survival and greater incidence of acute toxicity and no 5-year overall survival difference compared with radiotherapy alone [9]
When we only considered patients who remained disease-free in the first 2 years for further analysis, compared to those who received concurrent chemoradiotherapy (CCRT), patients who received neoadjuvant chemotherapy followed by radiotherapy (NACT) had a higher risk for recurrence (HR = 2.57, 95% confidence interval (CI):1.02 to 6.47, p =0.046) (Figure 1C)
Summary
Combined radiotherapy and chemotherapy is considered the standard of care for locally advanced nasopharyngeal carcinoma (LA-NPC) in Epstein-Barr virus infection endemic area. For locally advanced NPC, combined chemotherapy with RT may prolong overall survival with an absolute 5-year survival benefit of 4% [5,6,7]. Zhang et al reported that the relative benefit of this approach might be less in NPC-endemic area than that in non-NPC-endemic area [8] and Lee et al reported after median follow-up 5.9 years, the administration of cisplatin plus adjuvant cisplatin-fluorouracil concurrent with radiotherapy showed a better 5-year progression free survival and greater incidence of acute toxicity and no 5-year overall survival difference compared with radiotherapy alone [9]. The pivotal INT-0099 trial showed that 37% of patients in the concurrent chemoradiotherapy arm prematurely terminated the treatment because of excess toxicity [10]
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