Research in context
Evidence before this study
The aim of this study was to assess whether the addition of induction chemotherapy to standard concurrent chemoradiotherapy treatment provides further survival benefit in patients with locoregionally advanced nasopharyngeal carcinoma. We identified relevant studies through searches of PubMed and WHO’s International Clinical Trial Registry Platform for open or closed trials with a timeframe from database inception to June 8, 2016. Search terms included “nasopharyngeal carcinoma” or “cancer” or “neoplasm”, “neoadjuvant” or “induction chemotherapy”, and “chemoradiotherapy”. The search was limited to randomised clinical trials, with no language restrictions. So far, only three trials comparing concurrent chemoradiotherapy with induction chemotherapy followed by concurrent chemoradiotherapy have been published and the results are controversial. A phase 2 study comparing concurrent chemoradiotherapy alone with induction docetaxel and cisplatin followed by concurrent chemoradiotherapy reported improved overall survival in the induction chemotherapy plus concurrent chemoradiotherapy group. In another phase 2 trial, induction chemotherapy of cisplatin, epirubicin, and paclitaxel followed by concurrent chemoradiotherapy did not significantly improve overall survival or progression-free survival compared with concurrent chemoradiotherapy alone in stage IIB–IVB nasopharyngeal carcinoma. A randomised phase 2–3 trial comparing concurrent chemoradiotherapy alone with induction gemcitabine, carboplatin, and paclitaxel followed by concurrent chemoradiotherapy in stage III–IVB nasopharyngeal carcinoma did not record any significant improvements in survival. In three Bayesian network meta-analyses comparing concurrent chemoradiotherapy alone with induction chemotherapy plus concurrent chemoradiotherapy in nasopharyngeal carcinoma, the efficacies all seemed similar, except that induction chemotherapy plus concurrent chemoradiotherapy was associated with reduced distant metastasis. However, none of these trials used docetaxel, cisplatin, and fluorouracil (TPF), which has been shown to be an effective induction chemotherapy regimen for head and neck cancer. Besides this study (NCT01245959), several phase 3 randomised trials are also assessing the therapeutic benefits of adding different induction regimens to concurrent chemoradiotherapy (NCT00201396, NCT00705627, NCT01872962), and the results are awaited. From the aforementioned evidence, the efficacy of induction chemotherapy followed by concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma remains unclear and needs evidence from large-scale, randomised controlled trials.
Added value of this study
To the best of our knowledge, this is the first phase 3 study to assess the value of adding TPF induction chemotherapy to concurrent chemoradiotherapy in nasopharyngeal carcinoma. Our results show that compared with concurrent chemoradiotherapy alone, TPF induction chemotherapy followed by concurrent chemoradiotherapy significantly increases failure-free survival, overall survival, and distant failure-free survival with acceptable toxicity.
Implications of all the available evidence
This study suggests that adding TPF induction chemotherapy to concurrent chemoradiotherapy could improve survival and reduce distant failure in locoregionally advanced nasopharyngeal carcinoma. We recommend TPF induction chemotherapy followed by concurrent chemoradiotherapy to patients with advanced nasopharyngeal carcinoma; however, long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy.