In a Chinese phase III trial reported in The Lancet Oncology, Xing Lv, MD, and colleagues found noninferior progression-free survival with induction therapy with the third-generation platinum lobaplatin/fluorouracil (5-FU) vs cisplatin/5-FU, followed by lobaplatin- vs cisplatin-based chemoradiotherapy, in patients with previously untreated stage III to IVB nasopharyngeal carcinoma. Lobaplatin-based treatment was also associated with reduced toxicities.
As related by the investigators, previous clinical and preclinical findings indicate that lobaplatin may reduce toxicity vs cisplatin and may overcome multidrug resistance caused by other platinums.
The open-label multicenter trial included 502 patients aged 18 to 60 with previously untreated, nonkeratinizing stage III to IVB nasopharyngeal carcinoma. They were randomly assigned between June 2013 and June 2015 to receive induction with lobaplatin/5-FU (n = 252) or cisplatin/5-FU (n = 250) followed by concurrent lobaplatin-based vs cisplatin-based chemoradiotherapy. Induction therapy consisted of two cycles of lobaplatin at 30 mg/m² on days 1 and 22 and 5-FU at 800 mg/m² on days 1 to 5 and 22 to 26, or cisplatin at 100 mg/m² on days 1 and 22 and the same 5-FU regimen. Chemoradiotherapy consisted of two cycles of lobaplatin at 30 mg/m² or cisplatin at 100 mg/m² every 3 weeks plus intensity-modulated radiotherapy.
The primary endpoint was 5-year progression-free survival analyzed in both the intention-to-treat and per-protocol populations; the per-protocol population consisted of 246 patients in the lobaplatin-based group vs 237 in the cisplatin-based group who started chemoradiotherapy. Noninferiority was achieved if the upper limit of the 95% confidence interval (CI) for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%.
Median follow-up was 75.3 months (interquartile range = 69.9–81.1). In the intention-to-treat population, 5-year progression-free survival was 75.0% (95% CI = 69.7%–80.3%) in the lobaplatin-based group vs 75.5% (95% CI = 70.0%–81.0%) in the cisplatin-based group (hazard ratio [HR] = 0.98, 95% CI = 0.69–1.39, P = .92), with a difference of 0.5% (95% CI = –7.1% to 8.1%, P for noninferiority = .0070).
In the per-protocol population, 5-year progression-free survival was 74.8% (95% CI = 69.3%–80.3%) in the lobaplatin-based group and 76.4% (95% CI = 70.9%–81.9%) in the cisplatin-based group (HR = 1.04, 95% CI = 0.73–1.49, P = .83), with a difference of 1.6% (95% CI = –6.1% to 9.3%, P for noninferiority = .016).
Grade 1 to 2 adverse events that were significantly less common with lobaplatin vs cisplatin (all P < .0001) included nausea (42% vs 75%), vomiting (21% vs 60%), nephrotoxicity (21% vs 37%), and weight loss (32% vs 66%). Grade 3 to 4 adverse events occurred in 63% of the lobaplatin-based group vs 73% of the cisplatin-based group, with the most common being mucositis (41% vs 40%), leucopenia (16% vs 23%, P = .045), and neutropenia (10% vs 24%, P < .001).
The investigators concluded, “The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma.”