Which neoadjuvant chemotherapy regimen should be recommended for patients with advanced nasopharyngeal carcinoma?: A network meta-analysis

Abstract

Background: The clinical application has widespread disagreement on the different regimens of neoadjuvant chemotherapy (NCT) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). We conducted a network meta-analysis (NMA) to evaluate the efficacy of the different NCT regimens in the treatment of NPC.

Methods: A systematic literature search was performed using PubMed, Embase, and Cochran Library. Totally, 31 randomized controlled trials (RCTs) (n = 4062) met study selection criteria and were incorporated in this NMA study.

Results: Our study showed that certain NCT regimens improved the prognosis of patients, and found out the relative best solution for each endpoint, such as paclitaxel, carboplatin, and gemcitabine for 1-year overall survival (OS) rate, cisplatin, calcium folinate, and 5-fluorouracil for 2-year OS rate, vinorelbine and cisplatin (NP) for 3-year OS rate, cyclophosphamide, cisplatin, and 5-fluorouracil for 5-year OS rate, NP for complete remission rate, cisplatin and gemcitabine for overall remission rate of the primary tumor. In addition, for certain grade 3 and above toxicity, the results of the NMA reflected certain NCT regimens can reduce toxicity of chemoradiotherapy (CRT) to a minimum, such as NP for anemia, mucositis, and thrombocytopenia, paclitaxel, epirubicin, and cisplatin for neutropenia and skin toxicity.

Conclusion: Our NMA showed that certain cisplatin-based NCT regimens improved the prognosis of patients with NPC and reduced the toxicity of CRT. However, in view of survival rate and response rate, the best NCT regimen is not entirely consistent. Therefore, which NCT regimen will benefit most patients will need further explored.

Figure 1

Flow chart shows the detailed procedures of study screening and exclusion criteria. Thirty-one studies were included in this network meta-analysis. RCT = randomized controlled trial.

Figure 2

Evidence network of all enrolled studies in relation to short-term effects and survival outcomes in this network meta-analysis. (A) Network plot of complete remission rate (CRR) of primary tumor. (B) Network plot of overall remission rate (ORR) of primary tumor. (C) Network plot of 1-year overall survival (OS) rate. (D) Network plot of 2-year OS rate. (E) Network plot of 3-year OS rate. (F) Network plot of 5-year OS rate.

Figure 3

Evidence network of all enrolled studies in relation to toxicities (≥grade 3) in this network meta-analysis. (A) Network plot of anemia. (B) Network plot of neutropenia. (C) Network plot of skin toxicity. (D) Network plot of mucositis toxicity.

Figure 4

Ranking for the short-term effects in this network meta-analysis. (A) Complete remission rate (CRR) of primary tumor. (B) Overall remission rate (ORR) of primary tumor.

Figure 5

Ranking for the survival outcomes in this network meta-analysis. (A) 1-year overall survival (OS) rate. (B) 2-year OS rate. (C) 3-year OS rate. (D) 5-year OS rate.

Figure 6

Comparison-adjusted funnel plot for assessing publications bias. The red line suggests the null hypothesis that the study-specific effect sizes do not differ from the respective comparison-specific pooled effect estimates. Different colors represent different comparisons. (A) RT/CRT, (B) BCE-RT/CRT, (C) TPF-RT/CRT, (D) PF-RT/CRT, (E) DF-RT/CRT; (F) PE-RT/CRT, (G) CEP-RT/CRT, (H) TP-RT/CRT, (I) NP-RT/CRT, (J) PLF-RT/CRT, (K) BFC-RT/CRT, (L) CPF-RT/CRT, (M) PG-RT/CRT. BCE = bleomycin, epirubicin, and cisplatinum, BFC = bleomycin, 5-fluorouracil, and cisplatinum, CEP = paclitaxel, epirubicin, and cisplatin, CPF = cyclophosphamide, cisplatin, and 5-fluorouracil, CRT = chemoradiotherapy, DF = docetaxel and cisplatin, NP = vinorelbine and cisplatin, PE = cisplatin and epirubicin, PF = cisplatin and 5-fluorouracil, PG = cisplatin and gemcitabine, PLF = cisplatin, calcium folinate, and 5-fluorouracil, RT = radiotherapy, TP = docetaxel and cisplatin, TPF = docetaxel, cisplatin, and 5-fluorouracil.