Proteasome inhibitor bortezomib & re-irradiation (rRT) with scheduled treatment break in patients (pts) with head/neck squamous carcinoma (HNSCC)

5592 Background: We & others have previously shown that bortezomib inhibits activation of NFκB & other survival effectors & has cytotoxic, radiosensitizing, & anti-tumor activity in preclinical HNSCC models. A previous NCI phase 1 study evaluating dose escalation of bortezomib with rRT established a maximum tolerable dose (MTD) of 0.6 mg/m2 twice weekly IV with daily rRT for 6.6 weeks (60–70 Gy) based on dose limiting toxicity (DLT) of grade 3 hyponatremia & hypotension in 2 pts. The current study was designed to further explore the MTD & best tolerated schedule of bortezomib with rRT by introducing a treatment break. Methods: Pts with recurrent or metastatic HNSCC in whom rRT was feasible, who were ≥ 6 months since prior RT, had PS ≤2, AST/ALT <2.5x normal, bilirubin <1.5x normal, adequate hematopoetic & renal function were enrolled. Bortezomib was administered twice weekly as an IV bolus at the 0.6 mg/m2 dose level with rRT 1.8 Gy/day to 60–72 Gy. A 2-week break in both drug & rRT was given halfway thro...