Factors contributing to the efficacy of concurrent–adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Combined analyses of NPC-9901 and NPC-9902 Trials

BackgroundThe current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional–fractionation radiotherapy plus concurrent–adjuvant chemotherapy as recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors.MethodsEligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RTi group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg/m2/day for 4 days) for three cycles. The median follow-up was 6.1 years.FindingsComparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival (p ⩽ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant (p ⩾ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0–1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively.InterpretationOur results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.