Patients with stage II to IVB nasopharyngeal carcinoma who were treated with nedaplatin-based concurrent chemoradiotherapy, achieved 5-year survival rates comparable to those of patients treated with cisplatin chemoradiotherapy, but with fewer toxic effects, shows a study in JAMA Network Open.
The findings confirm that , wrote authors who were led by Lin-Quan Tang, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, China.
While the National Comprehensive Cancer Network recommends radiotherapy administered concurrently with 100 mg/m2 of cisplatin every 3 weeks for patients with stage II to IVB nasopharyngeal carcinoma, the addition of cisplatin-based chemotherapy to radiotherapy increases the frequency of treatment-related toxic effects. They include severe gastrointestinal responses, hearing deficits, renal toxic effects, and neurotoxic effects, decreasing treatment adherence and patient quality of life. An antitumor drug with similar therapeutic efficacy to cisplatin but with reduced adverse effects is needed urgently, authors wrote.
The cisplatin analogue nedaplatin, designed to decrease the nephrotoxic and gastrointestinal toxic effects seen with cisplatin, has antitumor mechanisms and efficacy similar to cisplatin. It has demonstrated effectiveness and tolerability in various malignant tumors, and has, in vitro, shown potential as a radiosensitizing agent with nasopharyngeal carcinoma and cervical squamous cell carcinoma cells.
In the initial 2-year results of the phase 3 randomized trial in this population of patients with stage II to IVB nasopharyngeal carcinoma, nedaplatin-based concurrent chemoradiotherapy was noninferior to cisplatin-based concurrent chemoradiotherapy with differences of 1.9% and 1.0% (P = .005 and P = .002), in the intention-to-treat and per-protocol analyses of progression-free survival, respectively. Patients (n = 402) were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)– or cisplatin (100 mg/m2)–based chemotherapy every 3 weeks for three cycles concurrently with intensity-modulated radiotherapy. Information on long-term follow-up and late toxic effects was limited.
In the current analysis of 402 patients (about 25% female, median age 44.5 years), the intention-to-treat 5-year progression-free survival rate was 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for the nedaplatin group, with a difference of 1.6% (95% CI, −6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs. 88.8%; P = .63), distant metastasis–free survival (85.9% vs. 90.4%, P = .17), and locoregional relapse–free survival (92.6% vs. 89.6%; P = .17) rates.
The incidence of grade 3 and 4 auditory toxic effects was higher in the cisplatin group than in the nedaplatin group (35 [17.7%] vs. 21 [10.5%], P = .04). Also, the cumulative incidence of grade 3-4 auditory toxic effects was higher in the cisplatin group versus patients in the nedaplatin group (19.9% vs. 12.0%; P = .42). The odds ratio, in a post hoc regression analysis, for auditory toxic effects was 0.51 (0.51; 95% CI, 0.28-0.93; P = .03) for patients in the nedaplatin group.
The findings, the authors concluded, confirm that nedaplatin-based concurrent chemoradiotherapy could be an alternative to cisplatin-based concurrent chemoradiotherapy as doublet therapy for II to IVB nasopharyngeal carcinoma. The potential of nedaplatin in combination drug chemotherapy for nasopharyngeal carcinoma in the induction or adjuvant phase needs to be explored in further investigations, the authors added.
The study was funded by multiple grants; the study investigator reported no conflicts of interest.