Intensity-Modulated Radiotherapy Plus 2 Cycles of Concurrent Cisplatin Improved Low-Risk LA-NPC Outcomes


Patients with low-risk locoregionally advanced nasopharyngeal carcinoma who received 2 cycles of concurrent cisplatin plus intensity-modulated radiotherapy compared with 3 cycles had better survival and manageable toxicities.

Concurrent cisplatin for 2 cycles at 100 mg/m2 plus intensity-modulated radiotherapy vs 3 cycles has been identified as a potential alternative strategy for patients with low-risk locoregionally advanced nasopharyngeal carcinoma, according to a study published in the Journal of Clinical Oncology.

At the median follow-up of 37.7 months, the estimated 3-year progression-free survival (PFS) was 88.0% after 2 cycles of treatment vs 90.4% after 3 cycles group. This translated to a difference of 2.4% (95% CI, –4.3 to 9.1; Pnoninferiority = .14).

A total of 332 patients with stage III to IVb nasopharyngeal carcinoma were enrolled on the trial and randomly assigned to either the 2-cycle group (n = 166) or the 3-cycle group (n = 166). Baseline characteristics were well balanced between treatment groups.

All patients completed the intensity-modulated radiotherapy, with similar results between groups. A total of 99.4% of those in the 2-cycle group and 89.8% in the 3-cycle group completed protocol-defined chemotherapy. Dose continuation or reduction was necessary in 18.1% of patients in the 2-cycle group and 36.1% in the 3-cycle group, primarily due to myelosuppression or patient refusal. A third cycle of continued carboplatin was given to 7.8% of patients in the 3-cycle group, 1 week after completing the last day of radiotherapy delivery.

In the 2-cycle group, 12.0% of progression events occurred vs 10.2% in the 3-cycle group. Of note, distant metastases were a major regression pattern, with 1.8% of deaths occurring between groups because of progression.

Patients in either group did not have any significant differences in PFS (HR, 1.20; 95% CI, 0.63-2.29; Plog-rank = .59), overall survival (HR, 1.00; 95% CI, 0.20-4.94; Plog-rank = 1.00), cumulative incidence of locoregional relapse (HR, 1.15; 95% CI, 0.42-3.15; PFine-Gray = .79), and distant metastases (HR, 1.22; 95% CI, 0.53-2.82; PFine-Gray = .64).

In the 2-cycle group, 4.2% of patients had pretreatment plasma Epstein-Barr virus (pEBV) DNA level of more than 4000/L copies compared with 4.8% in the 3-cycle group. Of these patients, 3 had treatment failure. In the 2-cycle group, 98.2% vs 98.8% of patients in the 3-cycle group had undetectable pEBV DNA levels.

Acute grade 3/4 toxicities were observed in 74.7% of patients in the 2-cycle group and 80.0% in the 3-cycle group. Between either group, there were no treatment-related deaths. Grade 3 to 4 mucositis (24.8% vs 15.1%), hyponatremia (15.8% vs 8.4%), and dermatitis (5.5% vs 1.2%) were higher in the 3-cycle group compared with the 2-cycle group. Overall, patients in the 3-cycle group had significantly higher toxicity burden, as shown by mean T-scores of 10.57 (95% CI, 10.10-11.03) compared with 12.33 (95% CI, 11.88-12.78; P <.001) in the 2-cycle group.

Late toxicities of any-grade in the 3-cycle group and 2-cycle group, respectively, consisted of hearing impairment (35.2% vs 22.9%), dry mouth (78.8% vs 63.9%), and skin fibrosis (29.7% vs 18.7%), with grade 3 and 4 effects being comparable between the groups.

Valid questionnaires regarding quality of life were collected in 57.2% and 60.8% of patients in the 2- and 3-cycles groups, respectively,. In the 2-cycle group, patients reported having less insomnia and constipation, as well as having a better cognitive function. In the 3-cycle group, patients reported having more speech problems and xerostomia with sensory dysfunction on the boundary of significance.


Li XY, Luo DH, Guo L, et al. Deintensified chemoradiotherapy for pretreatment Epstein-Barr Virus DNA-selected low-risk locoregionally advanced nasopharyngeal carcinoma: a phase II randomized noninferiority trial. J Clin Oncol. 2022;40(11):1163-1173. doi:10.1200/JCO.21.01467

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