Lobaplatin-based induction plus chemoradiation was as effective as, and safer than, a cisplatin-based regimen in a phase 3 trial of more than 500 patients with advanced nasopharyngeal carcinoma.
The lobaplatin regimen proved to be a “promising alternative regimen to cisplatin-based treatment,” Xing Lv, MD, of Sun Yat-sen University Cancer Centre in Guangzhou, China, and colleagues wrote in The Lancet Oncology.
A lobaplatin-based regimen might be particularly attractive when cisplatin is contraindicated, according to authors of a related editorial.
Given the encouraging results in this trial, lobaplatin might even “overtake carboplatin” in cisplatin-ineligible patients, wrote the editorialists, Stefano Cavalieri, MD, and Lisa Licitra, MD, both of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano in Italy.
“Furthermore, the optimal treatment compliance in patients receiving lobaplatin [in the trial] suggests that this agent might be a good candidate for research into escalation strategies,” the editorialists wrote.
Study rationale
Cisplatin-based induction followed by concurrent chemoradiotherapy is a standard treatment option in the United States, recommended by National Comprehensive Cancer Network guidelines for stage II-IVB nasopharyngeal carcinoma.
However, cisplatin is associated with poor treatment compliance due to significant hematologic and nonhematologic side effects. Cisplatin also requires increased hydration for renal protection, increasing the risk of fluid overload.
“Safer and more effective platinum drugs are needed for the treatment of nasopharyngeal carcinoma,” the investigators wrote.
Carboplatin is an alternative available in the United States, but “the evidence supporting equivalence between cisplatin with carboplatin is still controversial” for nasopharyngeal cancer, the editorialists wrote.
Study details
The phase 3 study enrolled 502 patients from five hospitals in China. The patients had previously untreated, non-keratinizing stage III–IVB nasopharyngeal carcinoma and a Karnofsky performance status score of at least 70. The study excluded patients older than 60 years of age, and adequate renal, hematologic, and hepatic function were required.
Half of patients (n = 252) were randomized to induction with lobaplatin and fluorouracil for two cycles followed by concurrent therapy with lobaplatin for two cycles plus intensity-modulated radiotherapy. The other half of patients (n = 250) were randomized to cisplatin-fluorouracil induction for two cycles, followed by intensity-modulated radiotherapy plus two cycles of cisplatin.
The investigators opted for two-cycle chemotherapy instead of three cycles after observing good activity and safety with two cycles in a phase 2 trial.
Treatment compliance was better in the lobaplatin arm, with 91% of those patients completing two cycles of concurrent chemotherapy, compared with 84% of patients in the cisplatin arm.
The 5-year progression-free survival rate was 75% in the lobaplatin arm and 75.5% in the cisplatin arm in the intention-to-treat population (P noninferiority = .007).
In the per-protocol population, the 5-year progression-free survival rates were 74.8% with lobaplatin and 76.4% with cisplatin (P noninferiority = .016).
The most common grade 3-4 adverse events were mucositis (41% in the lobaplatin arm and 40% in the cisplatin arm), leukopenia (16% and 23%, respectively), and neutropenia (10% and 24%, respectively).
Grade 1-2 nephrotoxicity, nausea, vomiting, and weight loss were significantly less common with lobaplatin (P < .0001 for all).