RESUMEN
In this study, we aim to compare the progression-free survival (PFS) rates and side effects of induction chemotherapy based on docetaxel, cisplatin and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in patients with locoregionally-advanced nasopharyngeal carcinoma who received subsequent chemoradiotherapy. We randomly assigned 278 patients with stage III or IV NPC (without distant metastases) to receive either TPF or PF induction chemotherapy, followed by cisplatin-based chemoradiotherapy every 3 weeks and intensity-modulated radiation therapy for 5 days per week. After a minimum of 2 years follow-up, a PFS benefit was observed for TPF compared to PF, though this difference was not statistically significant (84.5% vs. 77.9%, Pâ¯=â¯.380). Due to increased frequencies of grade 3 or 4 neutropenia and diarrhea, significantly more patients in the TPF group required treatment delays and dose modifications. Our findings suggest that PF induction chemotherapy has substantially better tolerance and compliance rates than TPF induction chemotherapy. However, the treatment efficacy of PF is not superior to TPF induction chemotherapy in patients with locoregionally-advanced NPC (ClinicalTrials.gov number, NCT01536223).
RESUMEN
OBJECTIVE: Compare high- vs. low-dose TPF neoadjuvant chemotherapy with chemoradiotherapy in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Retrospective analysis of 210 stage III/IV NPC patients treated between April 1, 2012 and April 1, 2014; 138 received three cycles of high-dose TPF (H-TPF) every 3 weeks at Zhejiang Cancer Hospital and 72, three cycles of low-dose TPF (L-TPF) every 3 weeks at Sun Yat-Sen University Cancer Center. H-TPF was docetaxel (75 mg/m2; 1 h infusion), cisplatin (75 mg/m2; 0.5-3 h), then 5-fluorouracil (600 mg/m2/day; 4 days). L-TPF was docetaxel (60 mg/m2), cisplatin (65 mg/m2), then 5-fluorouracil (550 mg/m2/day; 5 days). All patients received chemoradiotherapy. RESULTS: During neoadjuvant chemotherapy, treatment delays were more frequent for H-TPF than L-TPF (33.3% vs. 19.4%; P = 0.034). During chemoradiotherapy, grade III-IV anemia, thrombocytopenia and neutropenia were more common for H-TPF than L-TPF (P < 0.001, P < 0.001, P = 0.048). Fewer patients in the H-TPF group finished two cycles of concurrent chemotherapy (81.2% vs. 100%, P < 0.001). Three-year PFS (84.5% vs. 80.6%, P = 0.484) and OS (91.1% vs. 93.5%, P = 0.542) were not significantly different between H-TPF and L-TPF. CONCLUSIONS: L-TPF neoadjuvant chemotherapy has substantially better tolerance and compliance rates and similar treatment efficacy to H-TPF neoadjuvant chemotherapy in locoregionally-advanced NPC.
RESUMEN
DNA methylation, the best known epigenetic marker, can be used as a prognostic biomarker in many cancers. We examined DNA methylation status and survival in nasopharyngeal carcinoma (NPC) patients. Aberrant DNA-methylated genes in 24 NPC tissues and 24 noncancer nasopharyngitis biopsy tissues (NCNBT) were identified using Illumina 450K BeadChip. Correlations between DNA methylation and clinical outcomes were evaluated using bisulfite pyrosequencing in 454 NPC patients. Genome-wide methylation analysis demonstrated that NPC tissues had distinct DNA methylation patterns compared with NCNBT. Among all significant CpG sites, 2,173 CpG sites with ß change ≥ 0.2 (1,880 hypermethylated, 293 hypomethylated) were identified (P < 0.05). A methylation gene panel comprising six hypermethylated genes was constructed with the average Z-score method. Patients in the training cohort with high methylation had poorer disease-free survival [DFS, HR, 2.26; 95% confidence interval (CI), 1.28-4.01; P, 0.005] and overall survival (OS, HR, 2.47; 95% CI, 1.30-4.71; P, 0.006) than those with low methylation. There were similar results in the validation (DFS, HR, 2.07; 95% CI, 1.17-3.67; P, 0.013; OS, HR, 1.83; 95% CI, 1.01-3.31; P, 0.046) and independent cohorts (DFS, HR, 1.94; 95% CI, 1.08-3.47; P, 0.026; OS, HR, 2.09; 95% CI, 1.10-3.98; P, 0.022). Analysis indicated that the methylation gene panel was an independent prognostic factor. Furthermore, patients with low methylation had a favorable response to concurrent chemotherapy with an improved DFS (P = 0.045) and OS (P = 0.031), whereas patients with high methylation did not benefit from concurrent chemotherapy. The six-hypermethylated gene panel was associated with poor survival in patients with NPC, demonstrating its potential usefulness as a prognostic biomarker to clinicians in NPC management.
