Weekly cisplatin fails to show fewer serious side effects in p16-negative head and neck cancer
Physicians typically use either a higher dose of cisplatin given every three weeks or a lower dose given weekly in combination with radiation to treat locally advanced head and neck cancer. However, before NRG-HN009, there was limited randomized evidence to determine which regimen provided the best balance of cancer control and treatment-related side effects.
A recent study, NRG-HN009, sought to compare the effects of weekly cisplatin treatment with radiation to the traditional every three weeks regimen in patients with p16-negative head and neck cancer. Despite the importance of this inquiry for patients with multiple health issues and lower tolerance for intensive treatment, the weekly cisplatin regimen did not demonstrate fewer serious side effects than the standard schedule.
Consequently, the p16-negative cohort did not proceed to the Phase III trial. These findings, presented at the 2026 American Society for Radiation Oncology Annual Meeting and published in the International Journal of Radiation Oncology*Biology*Physics, suggest that weekly cisplatin induces a similar burden of serious acute side effects compared to the standard regimen.
However, the two approaches did result in distinct profiles of adverse effects. The study, led by Dr. Paul Harari of the University of Wisconsin, included 234 patients with p16-negative squamous cell carcinoma of the head and neck, randomly assigned to receive either 70 Gy of radiation with 100 mg/m2 of cisplatin every three weeks or 70 Gy of radiation with 40 mg/m2 of cisplatin weekly.
The primary outcome was acute toxicity, measured by the T-score, which showed no significant difference between the groups. While the weekly cisplatin group experienced more nausea, dehydration, and acute kidney injury, the every three weeks group had higher rates of decreased white blood cell counts and magnesium levels. The six-month locoregional failure rates were 4.6% for the weekly cisplatin group and 9.6% for the every three weeks group.
These results emphasize the necessity for further research to develop personalized treatment strategies that can minimize toxicity while preserving effective cancer control for advanced head and neck cancer patients.
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