Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma

Abstract

added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear.OBJECTIVE To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma. DESIGN, SETTING, AND PARTICIPANTSThis randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1.INTERVENTIONS Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m 2 , day 1], intravenous cisplatin [60 mg/m 2 , day 1], and oral capecitabine [1000 mg/m 2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m 2 , day 1] and fluorouracil [800 mg/m 2 daily, days 1-5]), followed by chemoradiotherapy. MAIN OUTCOMES AND MEASURESThe primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety. RESULTS Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR,. Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile.

UpToDate®

“…In a phase III trial of IC with cisplatin plus paclitaxel and capecitabine (TPC) versus cisplatin plus fluorouracil in over 200 patients with locoregionally advanced NPC, TPC improved failure-free survival (84 versus 69 percent) and was well tolerated. Overall survival at three years was similar between groups (95 versus 89 percent) [4]. For patients with advanced NPC, while gemcitabine plus cisplatin continues to be our preferred IC regimen, we consider TPC to be one acceptable alternative option in this patient population.…”

Efficacy and safety of low concentration hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy: a pilot cohort study

“…However, the AEs of patients treated with CCRT are reported to increase significantly. Hyperemia and necrosis of nasopharyngeal mucosa is one of the AEs [15][16][17][18]. The failure to timely discharge necrotic tissue of the nasopharyngeal tract will influence the radiation dose distribution and the sensitivity of cancer cells to radiotherapy, and in severe conditions, it may affect the therapeutic efficacy for NPC patients [5,19].…”

Capecitabine—A “Permanent Mission” in Head and Neck Cancers “War Council”?

“…The study designed by Gao et al investigated the benefit of reducing the toxicity profile for a combined cisplatin–capecitabine induction regimen in NPCs. Data analysis in a group of 136 patients demonstrated the ability of the cisplatin–capecitabine combination regimen delivered in induction settings to reduce HNSCC therapy-associated toxicities [ 28 , 29 , 30 , 31 ].…”