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

Abstract

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. 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=540/240mg/m2) 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 ≤300mg/m2). Multivariable analysis (MVA) was performed to identify survival predictors. 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=380/160mg/m2; median follow-up 76years (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/m2 (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 ≤300mg/m2 (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). Adjuvant chemotherapy and total CDDP-D >300mg/m2 improved OS and RFS in stage IV but not stage II-III LA-NPC, mainly due to effect on LRC rather than DC.