<h3>Purpose/Objective(s)</h3> To assess whether increasing the cycles of induction chemotherapy (IC) improve the survival in locally advanced nasopharyngeal carcinoma (NPC). <h3>Materials/Methods</h3> Patients with previously untreated, histopathologically confirmed, stage II-IVA NPC, aged 18-70 years without severe comorbidities who achieved PR (partial response) or CR (complete response) after two cycles of IC were recruited into this prospective clinical trial. Eligible patients were randomly assigned (1:1) to group A (concurrent chemoradiotherapy) or group B (two additional cycles of IC followed by concurrent chemoradiotherapy). Induction chemotherapy consisted of intravenous docetaxel (60 mg/m² on day 1), intravenous cisplatin (60 mg/m²on day 1), and fluorouracil (600 mg/m² per day continuous infusion on day 1 to day 5) every 3 weeks (TPF). In this trial, intensity-modulated radiotherapy was mandatory for both groups. And cisplatin 40 mg/m² given intravenously weekly or 100 mg/m² every 3 weeks during concurrent chemoradiotherapy. The primary endpoint was overall survival calculated from randomization to death from any cause. This study was registered in the China Clinical Trial Center (ChiCTR-TRC-1800017109). <h3>Results</h3> From July 16, 2018, to September 6, 2021, 437 patients were screened. After the exclusion of 66 patients for ineligibility, 371 patients (median age, 46 years [IQR, 23-69 years]) were randomly assigned to the group A (n=186) or group B (n=185). At the last follow-up on January 21, 2022, the median follow-up time was 25.3 (IQR 3.5-41.3) months. All enrolled patients were included in the interim analysis. The demographic and clinical characteristics of the two groups at baseline were well balanced (p£¾.05). All patients finished scheduled treatment. The 2-year estimated overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS) in group A versus group B were 98.4% vs 97.8%, 94.1 % vs 95.1%,98.4% vs97.8%, 95.7% vs 97.3%, respectively(p£¾.05). All patients received four cycles IC (group B) had higher incidences of leukopenia (P = .029), vomiting (P = .004), weigh loss(P=0.062) and thrombocytopenia (P = .043) than those treated with two cycles (group A). However, there was no difference in the incidence of late radiation toxicities between two groups. For advanced N (N3 and N2 who underwent lymph node biopsy) stage patients, we conducted a stratified analysis. The 2-year OS, DMFS of these patients in group A and group B were 96.6% and 98.7% (p=.687),94.4% and 97.3% (p=.275), group B has a trend of better survival. <h3>Conclusion</h3> In conclusion, the interim results demonstrate that increasing the cycles of IC with TPF to a mainstay of chemoradiotherapy with cisplatin did not improve the OS for locally advanced nasopharyngeal carcinoma, but it has the potential to reduce distant metastases for advanced N stage patients. These findings warrant validation with continuation of this trial and longer follow-up periods.
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