Impact of cumulative cisplatin dose and adjuvant chemotherapy in locally-advanced nasopharyngeal carcinoma treated with de finitive chemoradiotherapy

Background: Both adjuvant chemotherapy and higher cumulative cisplatin dose (CDDP-D) given as part of multimodality therapy for locally-advanced nasopharyngeal carcinoma (LA-NPC) have improved survival in Asian series. We evaluated their impact in a contemporary single-institution Canadian cohort of LA-NPC. Methods: Patients with EBV-related stage II-IV LA-NPC by 7th edition TNM (TNM-7) treated with IMRT plus high-dose CDDP followed by adjuvant chemotherapy with CDDP/Carboplatin - 5-FU (maximum total/adjuvant CDDP-D = 540/240 mg/m(2')) between 2003 and 2016 were analyzed. 5-year overall survival (OS) and recurrence-free survival (RFS) were calculated and compared using log-rank test by stage, adjuvant chemotherapy (yes/no) and total CDDP-D (> 300 vs <= 300 mg/m(2)). Multivariable analysis (MVA) was performed to identify survival predictors. Results: A total of 312 patients were evaluated: TNM-7 stage II/III/IV = 2%/51%/47%; T4 = 36%; N3 = 17%; adjuvant chemotherapy = 83% (79% 21% CDDP/carboplatin); median total/adjuvant CDDP-D = 380/160 mg/m(2); median follow-up 76 years (range 06-149). 5-year OS differed by stage II-III vs IV (95% vs 80%, p < 0.001) and by total CDDP-D > 300 (n = 210) vs <= 300 (n = 102) mg/m(2) (89% vs 83%, p = 0.02). Adjuvant chemotherapy and total CDDP-D impacted on 5-year OS in stage IV but not stage II-III. 5-year RFS was higher in stage IV patients with total CDDP-D > 300 vs <= 300 mg/m(2) (74% vs 59%, p = 0.03), with a trend seen in locoregional (LRC) (91% vs 80%, p = 0.05) but not distant control (DC) (78% vs 72%, p = 0.36). Conclusions: Adjuvant chemotherapy and total CDDP-D > 300 mg/m(2) improved OS and RFS in stage IV but not stage II-III LA-NPC, mainly due to effect on LRC rather than DC.