Two Versus Three Cycles of Induction Chemotherapy Show Similar Survival Outcomes in Advanced Nasopharyngeal Carcinoma
核心洞察
A retrospective analysis of 491 patients with locoregionally advanced nasopharyngeal carcinoma (搜索) found no significant survival differences between two and three cycles of induction chemotherapy.
Three cycles of induction chemotherapy achieved higher objective response rates (90.5% vs. 83.7%) but significantly increased mild to moderate toxicities including leukopenia (搜索), neutropenia (搜索), anemia (搜索), and vomiting.
The 5-year overall survival rates were comparable between groups (81.0% vs. 84.0%), suggesting two cycles may be sufficient while minimizing treatment-related complications.
A comprehensive retrospective analysis of 491 patients with locoregionally advanced nasopharyngeal carcinoma (搜索) (LANPC) has revealed that extending induction chemotherapy from two to three cycles does not improve survival outcomes while increasing treatment-related toxicities. The findings, published in BMC Cancer, challenge current clinical practices where approximately two-thirds of patients receive three cycles of induction therapy.
Treatment Response and Survival Outcomes
The study, conducted at the First Affiliated Hospital of Xiamen University (搜索) from January 2015 to December 2021, included 166 patients (33.8%) who received two cycles and 325 patients (66.2%) who received three cycles of induction chemotherapy. Patients with stage IVA disease, advanced T stage, and advanced N stage were more likely to receive three cycles of treatment.
While three cycles of induction chemotherapy achieved a significantly higher objective response rate compared to two cycles (90.5% vs. 83.7%, P = 0.029), this improvement did not translate into better long-term survival outcomes. The 5-year survival rates were comparable between groups across all endpoints: locoregional recurrence-free survival (88.6% vs. 89.9%), distant metastasis-free survival (79.2% vs. 83.1%), progression-free survival (70.5% vs. 73.2%), and overall survival (81.0% vs. 84.0%).
Cox proportional hazards regression analyses confirmed that patients receiving three cycles had comparable outcomes to those receiving two cycles: LRFS (HR 0.992, 95% CI 0.525–1.875, P = 0.981), DMFS (HR 0.805, 95% CI 0.511–1.092, P = 0.351), PFS (HR 0.917, 95% CI 0.633–1.328, P = 0.645) and OS (HR 0.880, 95% CI 0.552–1.402, P = 0.590).
Treatment Regimens and Patient Characteristics
The majority of patients were male (74.9%) with WHO III subtype disease (87.6%). Treatment regimens included the TP regimen (docetaxel plus cisplatin) in 70.9% of patients, followed by TPF (docetaxel, cisplatin, and 5-fluorouracil) and GP (gemcitabine plus cisplatin) regimens. All patients subsequently received intensity-modulated radiotherapy combined with concurrent chemoradiotherapy.
Stratified analysis across different induction chemotherapy regimens showed consistent results. In the GP cohort (n = 65), no significant differences were observed between two and three cycles across all survival endpoints. Similarly, in the TP/TPF cohort (n = 426), comparable outcomes were noted between treatment groups for all survival measures.
Toxicity Profile
A critical finding was the increased toxicity burden associated with three cycles of induction chemotherapy. While no significant differences were observed in Grade 3-4 acute toxicities between groups, three cycles significantly increased the incidence of Grade 1-2 toxicities: leukopenia (搜索) (P = 0.001), neutropenia (搜索) (P = 0.015), anemia (搜索) (P = 0.017), and vomiting (P = 0.024).
The median interval between the final induction chemotherapy cycle and radiotherapy initiation was similar between groups (21.5 vs. 21.6 days), suggesting that treatment delays did not confound the results.
Chemoimmunotherapy Advances
Complementing these findings, a separate meta-analysis involving 1,680 patients from seven studies demonstrated the emerging role of induction chemoimmunotherapy in locally advanced nasopharyngeal carcinoma (搜索). The analysis showed that induction chemoimmunotherapy significantly improved objective response rates (OR = 2.03, 95% CI: 1.44–2.86, P < 0.01) and complete response rates (OR = 2.61, 95% CI: 1.55–4.38, P < 0.01) compared to induction chemotherapy alone.
The pooled objective response rate and complete response rate for induction chemoimmunotherapy were 92.7% (95% CI: 90.7–94.7%) and 24.3% (95% CI: 15.2–33.6%), respectively. Importantly, there was no significant difference in treatment-related adverse events between induction chemotherapy and chemoimmunotherapy groups (OR = 1.13; 95% CI: 0.92–1.39, P = 0.23).
Clinical Implications
The findings suggest that two cycles of induction chemotherapy may be sufficient for LANPC patients, potentially minimizing treatment-related complications without compromising survival benefits. This approach could improve patient quality of life and treatment compliance while reducing healthcare costs.
The inherent radiosensitivity of nasopharyngeal carcinoma (搜索) suggests that subsequent radiotherapy may yield comparable efficacy in patients who have achieved either complete or partial response through induction chemotherapy. Previous prospective clinical trials have demonstrated that patients attaining complete response or partial response during induction chemotherapy experienced significantly improved survival outcomes compared to those with stable disease, while no significant survival difference was observed between complete response and partial response patients.
Study Limitations and Future Directions
The retrospective nature of the study may introduce selection bias and confounding factors. Additionally, the data originated from a single center in an endemic area and may not be representative of broader populations or patients in non-endemic areas. The relatively short follow-up period for some patients might limit the detection of long-term differences in survival outcomes.
Future prospective studies in well-defined patient groups with more uniform treatment programs differing only in the number of induction chemotherapy cycles are warranted. With the increasing use of immunotherapy in LANPC, future investigations should also explore the impact of different numbers of induction chemoimmunotherapy cycles on complete response rates and long-term survival outcomes.