Deintensified Chemoradiotherapy for Pretreatment Epstein-Barr Virus DNA-Selected Low-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Randomized Noninferiority Trial.

Abstract

PURPOSE:

Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL.

PATIENTS AND METHODS:

Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc.

RESULTS:

Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life.

CONCLUSION:

Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

• Authors: Xiao-Yun Li, Dong-Hua Luo, Ling Guo, Hao-Yuan Mo, Rui Sun, Shan-Shan Guo, Li-Ting Liu, Zhen-Chong Yang, Jin-Hao Yang, Fang Qiu, Xue-Song Sun, Pan Wang, Qing Liu, Ji-Bin Li, Qing-Nan Tang, Chao Lin, Qi Yang, Sai-Lan Liu, Yu-Jing Liang, Guo-Dong Jia, Dong-Xiang Wen, Chun-Yan Guo, Jin-Jie Yan, Chong Zhao, Qiu-Yan Chen, Lin-Quan Tang, Hai-Qiang Mai
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 40 Issue 11 Pg. 1163-1173 (04 10 2022) ISSN: 1527-7755 [Electronic] United States
• PMID: 34990291 (Publication Type: Clinical Trial, Phase II, Equivalence Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• DNA
• Cisplatin

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Chemoradiotherapy (adverse effects)
• Cisplatin
• DNA (therapeutic use)
• Epstein-Barr Virus Infections
• Herpesvirus 4, Human (genetics)
• Humans
• Nasopharyngeal Carcinoma (drug therapy)
• Nasopharyngeal Neoplasms (pathology)
• Neoplasm Recurrence, Local (drug therapy)
• Quality of Life
• Retrospective Studies