Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long‐term results of phase 3 randomized controlled trial

Abstract

To report long‐term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III–IVB (except T3–4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2/d civ d1–5) every 3 weeks. Patients from both groups received intensity‐modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow‐up of 71.5 months, the IC plus CCRT group showed significantly better 5‐year failure‐free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure‐free survival (88% vs. 79.8%, p = 0.030), and locoregional failure‐free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein–Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long‐term follow‐up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.

Induction Chemotherapy Improved Long Term Outcomes in Stage IV Locoregional Advanced Nasopharyngeal Carcinoma

“…If we count the entire LANPC cohort, the overall results of the OS and FFS rates were similar to other published series [11,12] with better DMFS in the IC + CCRT group. However, there were distinct results if the outcomes for the stage III and stage IV LANPC cases were calculated separately.…”

“…Docetaxel (T), cisplatin (P), and 5-fluorouracil (F) (TPF regimen) IC + CCRT method has been shown to improve 3-year FFS, OS, and distant metastasis-free survival (DMFS) when compared with the CCRT alone method in LANPC [10]. Their 5-year outcome results confirmed the conclusion in the same groups of patients [11]. Recently, gemcitabine (G) and P IC was shown to be as efficient as TPF in treating LANPC in a randomized study [12].…”

“…The more advanced the stage, the greater the risk of occult distant metastasis (DM) [16,17]. In addition, acute adverse events and low grade chronic peripheral neuropathy have been found to be drawbacks of adding IC to CCRT [11,12]. Some authors have also highlighted the importance of selecting the right subgroups for IC addition [18,19].…”

Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1

“…Increasing evidence suggests that systemic induction chemotherapy (IC) can effectively eliminate NPC micrometastasis and ultimately improve patient survival [18][19][20]. However, the responses to chemotherapy are heterogeneous, and some patients can develop resistance, leading to treatment failure [20].…”

“…Increasing evidence suggests that systemic induction chemotherapy (IC) can effectively eliminate NPC micrometastasis and ultimately improve patient survival [18][19][20]. However, the responses to chemotherapy are heterogeneous, and some patients can develop resistance, leading to treatment failure [20]. Currently, the recommended tumornode-metastasis (TNM) staging system is not effective enough to predict ideal candidates for chemotherapy among NPC patients, which highlights the urgent need to explore new biomarkers for determining treatment [1,6].…”