Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area

Cancer Res Treat. 2018 Jul;50(3):777-790. doi: 10.4143/crt.2017.255. Epub 2017 Jul 24.

Abstract

Purpose: The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC).

Materials and methods: Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1-induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1-induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS.

Results: Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel-cisplatin-5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin-5-fluorouracil (PF) (PF and docetaxel-cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1-induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect.

Conclusion: Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

Keywords: Lymphocyte; Nasopharyngeal carcinoma; Neutropenia; Prognosis; Survival; Induction chemotherapy.

MeSH terms

  • Adult
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Docetaxel
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Induction Chemotherapy / adverse effects*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Staging
  • Neutropenia / chemically induced*
  • Prognosis
  • Survival Analysis
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Young Adult

Substances

  • Taxoids
  • Docetaxel
  • Cisplatin
  • Fluorouracil