Inhibition of nuclear factor-κB and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma

摘要: Purpose: To examine the effects proteasome inhibitor bortezomib (VELCADE) on transcription factor nuclear factor-κB (NF-κB) and target genes feasibility of combination therapy with reirradiation in patients recurrent head-and-neck squamous cell carcinoma (HNSCC). Methods Materials: The tolerability response to 0.6 mg/m 2 0.9 given twice weekly concurrent daily 50–70 Gy was explored. Blood inhibition NF-κB–modulated cytokines factors were measured. Proteasome inhibition, localization NF-κB phospho-p65, apoptosis, expression mRNAs compared serial biopsies from accessible tumors. Results: maximally tolerated dose exceeded, study limited 7 patients, respectively, /dose reirradiation. Grade 3 hypotension hyponatremia limiting. Mucositis or less delayed. mean blood at 1, 24, 48 h after 32%, 16%, 7% 56%, 26%, 14%, respectively. Differences activity, cycle, angiogenesis detected minor tumor reductions serum 1 patient a major reduction. Conclusions: In reirradiation, exceeded threshold inhibition. Although this regimen is not feasible, induced detectable differences localization, association reduction, indicating that other schedules combined primary radiotherapy may merit future investigation.