Generational toxicity.

Top Line: Do next-generation platinum drugs reduce toxicity compared to cisplatin for head and neck cancers?

The Study: Multiple randomized trials have shown improved overall survival when induction chemo is added to concurrent chemoradiation for locally advanced nasopharyngeal carcinoma (NPC). Platinum is the backbone of these induction regimens and is often seen in a doublet regimen with 5FU or gemcitabine or in a triplet regimen with docetaxel and 5FU. Yet, cisplatin toxicity can be considerable. This randomized phase 3  non-inferiority trial sought to determine if replacement of cisplatin with lobaplatin, a third-generation platinum drug, resulted in less toxicity and non-inferior disease outcomes in 502 patients with locally advanced NPC. The overall treatment regimen consisted of two cycles of induction platinum + 5FU ( instead of the typical three cycles of induction chemotherapy) and two cycles of concurrent platinum with radiation. Patients were randomized to either 100 mg/m2 cisplatin or 30 mg/m2 lobaplatin as their platinum agent. Radiation consisted of a four-volume simultaneous integrated boost approach with the primary tumor receiving 68-70 Gy, gross nodes 62-68 Gy, high risk CTV 60 Gy, and low risk CTV 54 Gy all in 30-32 fractions. At 5 years, there was no difference in the rate of PFS with lobaplatin (75%) vs cisplatin (75.5%). There was also no difference in 5-year OS (88% vs 89%), locoregional recurrence free survival (88% vs 89%), or DM-free survival (87% vs 85%). Rates of grade 3+ neutropenia, anemia, nausea, and vomiting were all lower with lobaplatin. In addition, lobaplatin also had less low-grade toxicity and less late peripheral neuropathy.

TBL: Lobaplatin, a next generation platinum, appears to have less toxicity than cisplatin while maintaining non-inferior disease outcomes among patients receiving induction chemo and chemoradiation for NPC. | Lv, Lancet Oncol 2021