Addition of 5-fluorouracil to docetaxel/cisplatin does not improve survival in locoregionally advanced nasopharyngeal carcinoma

Addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) is a potentially effective approach for treating locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we compared the efficacy and toxicity of IC regimens consisting of docetaxel plus cisplatin with (TPF) or without (TP) 5-fluorouracil followed by CCRT in these patients. Clinical data from 245 propensity score-matched pairs of newly diagnosed non-metastatic NPC patients who received either TPF or TP IC before CCRT were retrospectively reviewed. After a median follow-up of 60 months, 5-year locoregional relapse-free, distant metastasis-free, progression-free, and overall survival rates were 95.6%, 94.7%, 90.4%, and 92.9% in TPF arm patients and 96.7%, 94.2%, 91.7%, and 91.0% in TP arm patients, respectively. There were thus no differences in survival between the two arms. Multivariate analysis revealed that IC regimen was not an independent prognostic factor for any of the survival outcomes. However, patients who received TP experienced lower incidences of grade 3/4 toxicities than those who received TPF. These results indicate that omission of 5-fluorouracil from TPF-based IC did not affect survival outcomes, but was associated with reduced toxicity, in patients with locoregionally advanced NPC.

[1]  Zhimin Ye,et al.  Association of the neoadjuvant chemotherapy cycle with survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma: a propensity-matched analysis , 2017, Oncotarget.

[2]  W. Lei,et al.  Addition of 5-fluorouracil to first-line induction chemotherapy with docetaxel and cisplatin before concurrent chemoradiotherapy does not improve survival in locoregionally advanced nasopharyngeal carcinoma , 2017, Oncotarget.

[3]  T. Onitsuka,et al.  Survival benefit of adding docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy to concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma with nodal Stage N2–3 , 2017, Japanese journal of clinical oncology.

[4]  Chaosu Hu,et al.  Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials , 2017, Cancer.

[5]  W. Lei,et al.  Gemcitabine/cisplatin induction chemotherapy before concurrent chemotherapy and intensity-modulated radiotherapy improves outcomes for locoregionally advanced nasopharyngeal carcinoma. , 2017, Oncotarget.

[6]  B. Long,et al.  Efficacy and safety of nimotuzumab with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma , 2017, Oncotarget.

[7]  S. Liang,et al.  Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. , 2016, The Lancet. Oncology.

[8]  E. Deutsch,et al.  Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by concurrent chemoradiotherapy or chemoradiotherapy alone in locally advanced non-endemic nasopharyngeal carcinoma. , 2016, Oral oncology.

[9]  J. Cui,et al.  Significant benefits of adding neoadjuvant chemotherapy before concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of randomized controlled trials , 2016, Oncotarget.

[10]  W. Xue,et al.  Global trends in incidence and mortality of nasopharyngeal carcinoma. , 2016, Cancer letters.

[11]  Ying Sun,et al.  Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials , 2015, Journal of Cancer.

[12]  Jun Ma,et al.  Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. , 2015, The Lancet. Oncology.

[13]  Y. Mao,et al.  Significant efficacies of neoadjuvant and adjuvant chemotherapy for nasopharyngeal carcinoma by meta-analysis of published literature-based randomized, controlled trials. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[14]  Yunfeng Zhou,et al.  Phase II trial of neoadjuvant docetaxel and cisplatin followed by intensity-modulated radiotherapy with concurrent cisplatin in locally advanced nasopharyngeal carcinoma , 2013, Cancer Chemotherapy and Pharmacology.

[15]  R. Sun,et al.  A randomized trial of induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus radiotherapy for locoregionally advanced nasopharyngeal carcinoma. , 2012, Oral oncology.

[16]  Y. Mao,et al.  The seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma is prognostically useful for patients treated with intensity-modulated radiotherapy from an endemic area in China. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[17]  T. Ciuleanu,et al.  Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[18]  J. Wee Nasopharyngeal cancer: a promising future. , 2012, The Lancet. Oncology.

[19]  B. O'Sullivan,et al.  Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. , 2010, Journal of the National Cancer Institute.

[20]  J. Hwang,et al.  Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer , 2010, Cancer Chemotherapy and Pharmacology.

[21]  G. Calais,et al.  Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. , 2009, Journal of the National Cancer Institute.

[22]  Peter C. Austin,et al.  The Relative Ability of Different Propensity Score Methods to Balance Measured Covariates Between Treated and Untreated Subjects in Observational Studies , 2009, Medical decision making : an international journal of the Society for Medical Decision Making.

[23]  A. King,et al.  Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  T. Gorlia,et al.  Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. , 2007, The New England journal of medicine.

[25]  A. Markoe,et al.  Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. , 2007, The New England journal of medicine.

[26]  J. Cooper,et al.  Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  Pelayo Vilar,et al.  Nasopharyngeal Carcinoma , 1966 .

[28]  W. Lei,et al.  Long-Term Use of Nimotuzumab in Combination With Intensity-Modulated Radiotherapy and Chemotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma: Experience of a Single Institution. , 2018, Oncology research.

[29]  Li-Zhi Liu,et al.  INTENSITY-MODULATED RADIOTHERAPY VERSUS CONVENTIONAL TWO-DIMENSIONAL RADIOTHERAPY INFLUENCE THE TREATMENT RESULTS IN NASOPHARYNGEAL CARCINOMA PATIENTS ? , 2011 .

[30]  K. Galal,et al.  Neo-adjuvant Docetaxel and Cisplatin followed by concurrent Cisplatin with radiation therapy in treatment of locally advanced nasopharyngeal carcinoma. , 2008, The Gulf journal of oncology.

[31]  A. Fathi,et al.  Neoadjuvant Docetaxel and Cisplatin followed by Concurrent Cisplatin with Radiation Therapy in Treatment of Locally Advanced Nasopharyngeal Carcinoma , 2007 .

[32]  J. Pignon,et al.  Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. , 2006, International journal of radiation oncology, biology, physics.