Phase I study of proteasome inhibitor bortezomib (B) concurrent with re-irradiation therapy (re-RT) for recurrent squamous cell carcinoma of the head and neck (SCCHN).

2603 Background: B demonstrated antitumor and radiosensitizing activity in preclinical solid tumor models. Methods: A phase I trial was designed to assess escalating doses of B 0.6, 0.9 or 1.2 mg/m2 IV twice weekly concurrent with re-RT 2Gy/5 days/wk to 60-70 Gy. Evaluations included standard measures for adverse events (CTC v3.0), tumor response (RECIST), progression-free survival (PFS) and overall survival (OS). Baroreceptor reflex testing was initiated in a subset of patients to assess the potential cause of observed orthostatic hypotension. Results: 25 patients with recurrent SCCHN were treated: 19 men, 6 women, median age 57 yrs, ECOG performance status∼1, prior surgery and chemotherapies∼1 and > 6 mos since prior RT. All were evaluable for toxicity and 19 for response. B 0.6 or 0.9 mg/m2 + re-RT given 2x/wk for 6-7 wks without breaks was associated with dose-limiting orthostatic hypotension and/or hyponatremia. Amended schedules with a mid-course 2-wk break from B and re-RT, or B alone, were better ...