In a Chinese phase III trial reported in JAMA Oncology, Li et al found that induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) prior to concurrent chemoradiation was associated with improved failure-free survival vs induction therapy with cisplatin and fluorouracil (PF) in patients with previously untreated stage IVA to IVB nasopharyngeal carcinoma.
Study Details
In the open-label multicenter trial, 238 patients were randomly assigned between October 2016 and August 2019 to receive induction therapy with two 21-day cycles of TPC (n = 118) or PF (n = 120). Random assignment was stratified by disease stage.
TPC consisted of paclitaxel at 150 mg/m2 on day 1, cisplatin at 60 mg/m2 on day 1, and capecitabine at 1,000 mg/m2 twice daily on days 1 to 14; PF consisted of cisplatin at 100 mg/m2 on day 1 and fluorouracil at 800 mg/m2 daily via continuous infusion on days 1 to 5. All patients then received two cycles of cisplatin at 100 mg/m2 concurrent with intensity-modulated radiotherapy.
The primary endpoint was failure-free survival (absence of recurrence or death) in the intention-to-treat population.
KEY POINTS
- Induction therapy with paclitaxel, cisplatin, and capecitabine was associated with improved failure-free survival vs cisplatin/fluorouracil.
- Failure-free survival at 3 years was 83.5% vs 68.9%.
Failure-Free Survival
Median follow-up was 48.4 months (interquartile range = 39.6–53.3 months). Failure-free survival at 3 years was 83.5% (95% confidence interval [CI] = 77.0%–90.6%) in the TPC group vs 68.9% (95% CI = 61.1%–77.8%) in the PF group (stratified hazard ratio [HR] = 0.47, 95% CI = 0.28–0.79, P = .004).
At 3 years, distant metastasis–free survival was 91.4% (95% CI = 86.4%–96.6%) vs 80.4% (73.6%–87.9%; stratified HR = 0.49, 95% CI = 0.24–0.98, P = .04) and locoregional relapse–free survival was 93.8% (95% CI = 89.5%–98.4%) vs 87.4% (95% CI = 81.4%–93.8%; stratified HR = 0.40, 95% CI = 0.18–0.93, P = .03). Death occurred in 5.1% vs 10.8% of patients, with a 3-year overall survival rate of 94.7% (95% CI = 90.6%–98.9%) vs 88.9% (95% CI = 83.4%–94.8%; stratified HR = 0.45, 95% CI = 0.17–1.18, P = .10).
Adverse Events
Acute treatment-related grade 3 or 4 adverse events occurred in 57.6% of patients in the TPC group vs 65.8% of the PF group. The most common in both groups were mucositis (28.0% vs 28.3%), vomiting (18.6% vs 15.8%), leukopenia (15.3% vs 14.2%), nausea (15.3% vs 20.8%), and neutropenia (12.7% vs 18.3%). Late treatment-related grade 3 or 4 adverse events occurred in 13.6% vs 17.9% of patients. One patient in the PF group died from treatment-related renal failure.
The investigators concluded, “This randomized clinical trial found that induction chemotherapy with two cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with two cycles of PF, with no increase in the toxicity profile.”
Yan-Qun Xiang, MD, and Wei-Xiong Xia, MD, of the Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou, are the corresponding authors for the JAMA Oncology article.
Disclosure: The study was supported by the National Natural Science Foundation of China. For full disclosures of the study authors, visit jamanetwork.com.
