Comparison of the efficacy and safety of the EXTREME regimen for treating recurrent or metastatic head and neck squamous cell carcinoma in older and younger adult patients.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a geriatric cancer. However, older adult patients are frequently underrepresented in large clinical trials. AIMS: The aim of this study is to assess the efficacy and safety of the EXTREME regimen (platinum + fluorouracil + cetuximab) in older and younger adult patients with HNSCC. METHODS AND RESULTS: Patients with recurrent or metastatic HNSCC treated with the EXTREME regimen were retrospectively analyzed. We compare the efficacy and safety in older (aged ≥70 years) younger (aged <70 years) adult patients. Of the 86 patients examined in this study, 21 (24.4%) were older adults. There was no difference in overall response rate (46.9% vs 38.5%, P = .76), median progression-free survival [5.7 months vs 5.8 months, hazard ratio (HR) 0.88, 95% confidence interval (CI) = 0.52-1.51, P = .66] and overall survival (OS) (14.6 months vs 15.2 months, HR 0.79, 95% CI 0.43-1.43, P = .44) in younger vs older patients. There was also no difference in the incidence of grade 3/4 adverse events between groups. The exploratory analysis for geriatric nutritional risk index (GNRI) showed the association with lower GNRI (≤98) and poor OS in older adult patients (37.7 months vs 7.0 months, HR 0.53, 95% CI 0.31-0.89, P = .002). CONCLUSIONS: The EXTREME regimen with optimal dose modification is safe and effective for both older and younger adult patients with HNSCC. The GNRI can be an indicator to select the older adult patients who can get benefit from the EXTREME regimen.

Suppression of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma through IKKß inhibition.

We explored the role of the transcription factor, NF-κB, and its upstream kinase IKKß in regulation of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). We showed that cisplatin-resistant HNSCC cells have a stronger ability to migrate and invade, as well as display higher IKKß/NF-κB activity compared to their parental partners. Importantly, we found that knockdown of IKKß, but not NF-κB, dramatically impaired cell migration and invasion in these cells. Consistent with this, the IKKß inhibitor, CmpdA, also inhibited cell migration and invasion. Previous studies have already shown that N-Cadherin, an epithelial-mesenchymal transition (EMT) marker, and IL-6, a pro-inflammatory cytokine, play important roles in regulation of HNSCC migration, invasion, and metastasis. We found that cisplatin-resistant HNSCC expressed higher levels of N-Cadherin and IL-6, which were significantly inhibited by CmpdA. More importantly, we showed that CmpdA treatment dramatically abated cisplatin-resistant HNSCC cell metastasis to lungs in a mouse model. Our data demonstrated the crucial role of IKKß in control of migration, invasion, and metastasis, and implicated that targeting IKKß may be a potential therapy for cisplatin-resistant metastatic HNSCC.