A phase II study of Lonafarnib (SCH66336) in patients with chemorefractory, advanced squamous cell carcinoma of the head and neck.

Objective: Treatment options for recurrent squamous cell carcinoma of the head and neck (SCCHN) following platinum-based therapy are limited. Lonafarnib is a potent, specific inhibitor of farnesyl transferase that demonstrated marked antitumor activity as monotherapy in treatment-naive SCCHN in a phase Ib study. A phase II study of lonafarnib was conducted to determine its efficacy and safety in patients with recurrent, platinum-refractory SCCHN.

Methods: This was an open-label, phase II, single-center study in patients with recurrent SCCHN after platinum-based therapy. A Simon 2-stage design was used, with a plan to close the study to further accrual if <2 of the first 15 patients had objective responses. Patients were treated with lonafarnib 200 mg twice daily (b.i.d.) by mouth continuously in 4-week cycles.

Results: Fifteen patients with baseline Eastern Cooperative Oncology Group PS 0-1 and median age 57 years were enrolled. Twelve patients had received at least 2 previous chemotherapy regimens. Median duration of treatment with lonafarnib was 61 days. No objective response was observed. Seven (47%) patients maintained stable disease through >or=3 cycles of therapy. Median time to progression and survival time were 2.04 and 9.17 months, respectively. Most treatment-related toxicities were grade 1-2, and there were no treatment-related deaths.

Conclusions: Lonafarnib at a dose of 200 mg b.i.d. was well-tolerated. However, there were no objective responses observed in the first 15 patients enrolled in this study, and the study was closed to further accrual, as per predefined criteria. Further evaluation of lonafarnib in platinum-refractory SCCHN is not planned.