Comparison of Induction Chemotherapy Versus Adjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma Treated with IMRT and Concurrent Cisplatin

Abstract

To compare the efficacy and toxicities of concurrent chemoradiation (CCRT) with adjuvant chemotherapy (ACT) (CCRT+ACT) versus induction chemotherapy (ICT) plus CCRT (ICT+CCRT) in locally advanced nasopharyngeal cancer (LANPC). Patients with stage III-IVB NPC (7th ed AJCC staging) treated from January 2011 to January 2017 at 3 centers in China were retrospectively reviewed. All patients were treated with IMRT with concurrent cisplatin (80 mg/m2 on day 1, 22, and 43). Three chemo regimens were used in ICT or ACT. They are PF (5 FU 500-750 mg/m2, continuous infusion 1-5 days, cisplatin 25 mg/m2, day 1-3), TP (docetaxel 75 mg/m2, day 1, and cisplatin 25 mg/m2, day 1-3), or TPF (docetaxel 60-75 mg/m2, day 1, cisplatin 20-25 mg/m2, day 1-3, and 5 FU 500-750 mg/m2, continuous infusion 1-5 days). Two to three cycles of chemo were delivered every 21 days. The primary endpoint was overall survival (OS). Secondary endpoints included locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and toxicities. Survivals were calculated with Kaplan-Meier method. The differences between survivals were calculated by Log-rank test. Toxic effects were analyzed using the χ2 test. All statistical tests were two-side. A total of 350 patients were identified and 301 were eligible for analysis. 155 patients were treated with ICT+CCRT and 146 with CCRT+ACT. With a median follow-up of 61.5 months (range:5.81-89.70 months), there was no significant difference between the ICT+CCRT group and CCRT+ACT group in 5-year OS (83.2% vs. 79.5%, p=0.190 ), LRFS (84.7% vs. 83.2%, p=0.486 ) or DMFS (78.9% vs. 74.3%, p=0.119 ). However, in patients with early T-stage and advanced N-stage disease (stage T1-2N2-3), ICT+CCRT significantly improved 5-year OS (84.1% vs. 74.6%, p=0.043) and DMFS (71.4% vs. 60.3%, p=0.039), but not LRFS (93.2% vs. 92.4%, p=0.624). There was no statistical difference in OS, LRFS, and DMFS between two groups in patients with advanced T-stage and early N-stage disease (stageT3-4N0-1) (81.7% vs.76.7%, p=0.535; 77.5% vs.73.3%, p=0.463; 84.0% vs. 79.4%, p=0.452, respectively). In the ICT+CCRT group, 43 patients received PF, 54 TP, and 58 TPF. There were no statistical differences in survivals between different chemo regimens. In the CCRT+ACT group, 83 patients received PF, 61 TP, and 2 TPF. Again, there were no statistical differences in survivals between different chemo regimens. In addition, there were no statistical differences in survivals with the same chemo regimen either it was given before or after CCRT. The grade 3 or 4 adverse events of two groups had no statistical difference in both hematologic and non-hematologic toxicities (P>0.05). There was no statistical difference in efficacy and toxicities between ICT+CCRT versus CCRT+ACT in LANPC. However, ICT+CCRT may be superior in patients with early T-stage and advanced N-stage disease (T1-2N2-3). Randomized trial may be warranted in this patient population.