5578 Background: SAHA is a potent histone deacetylase inhibitor that has excellent oral bioavailability. Preclinical studies demonstrated that SAHA has growth inhibitory and apoptosis-inducing activity in SCCHN cell lines in vitro. In a phase I trial of oral SAHA administered once a day or twice a day, a partial response was observed in a pt with metastatic laryngeal carcinoma. A phase II trial was initiated to assess the efficacy and safety of oral SAHA administered as 400 mg qd in pts with SCCHN. METHODS Eligible pts must have recurrent and/or metastatic SCCHN unresponsive to or intolerant of conventional chemotherapy (up to two prior chemotherapies including neoadjuvant, adjuvant, and concomitant chemotherapy/radiation); ECOG performance status 0-2; adequate hematologic, hepatic, and renal function; able to swallow capsules; have measurable disease; = 4 weeks from prior chemotherapy, radiation therapy, major surgery or investigational anticancer therapy and have recovered from prior toxicities. Study endpoints included response rate, duration of stable disease and progression-free survival. RESULTS 13 pts were enrolled (9 males, 4 females). 12 pts have received oral SAHA at 400 mg qd and were evaluable for response. 1 pt withdrew consent prior to starting therapy. Median age is 54 years (range 38-83). Prior therapies included radiation in 9 pts and chemotherapy in all 12 pts; 11 patients received platinum, 8 patients received both taxanes and platinum. No partial or complete responses were observed. Tumor shrinkage by CT scan (minor response) was seen in 1 pt. 4 pts had stable disease lasting 3 to 6 months. Toxicity has been acceptable with 1 pt discontinuing therapy for grade 3 anorexia. Other grade 3-4 drug-related toxicities included anemia (n=1), anorexia (n=1), back pain (n=1), fatigue (n=1), and thrombocytopenia (n=3). CONCLUSIONS SAHA at 400 mg qd appears to be well tolerated and has modest single agent activity in this small group of heavily pre-treated pts. In view of the signs of activity and good tolerability, a dose intense schedule will be tested. [Table: see text].