Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma - PDF Version
Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J.
N Engl J Med. 31 May 2019. doi: 10.1056/NEJMoa1905287. [Epub ahead of print]
BACKGROUND
Platinum-based concurrent chemoradiotherapy is the standard of care for patients with loco-regionally advanced nasopharyngeal carcinoma. Additional gemcitabine- and cisplatin-induction chemotherapy has shown promising efficacy in phase 2 trials.
METHODS
In a parallel-group, multicentre, randomised, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy agents plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with loco-regionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1g/m2 of body-surface area on days one and eight) plus cisplatin (80mg/m2 on day one), administered every three weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100mg/m2 every three weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or loco-regional recurrence]) or death from any cause in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety.
RESULTS
A total of 480 patients were included in the trial (242 patients in the induction-chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the three-year recurrence-free survival was 85.3% in the induction-chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at three years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grades 3 or 4 was 75.7% in the induction-chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anaemia, nausea, and vomiting in the induction-chemotherapy group. The incidence of grades 3 or 4 late toxic effects was 9.2% in the induction-chemotherapy group and 11.4% in the standard-therapy group.
CONCLUSION
Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with loco-regionally advanced nasopharyngeal carcinoma.