Treatment options for patients with advanced head and neck squamous cell carcinoma (HNSCC) are scarce. This phase 2 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and efficacy of dasatinib in this setting.

Patients with recurrent and/or metastatic HNSCC after platinum‐based therapy were treated with dasatinib either orally or via percutaneous feeding gastrostomy (PFG). Primary endpoints were 12‐week progression‐free survival (PFS) and objective response rate with a 2‐stage design and early withdrawal if the 12‐week PFS rate was ≤20% and no patients had an objective response (OR). Forty‐nine serum cytokines and angiogenic factors (CAFs) were analyzed from treated patients.

Of the 15 patients enrolled, 12 were evaluable for response, and all patients were evaluable for toxicity. No OR was observed and 2 patients (16.7%) had stable disease (SD) at 8 weeks. The median treatment duration was 59 days, the median time to disease progression was 3.9 weeks, and the median survival was 26 weeks. One patient required a dose reduction, 3 patients required dose interruptions, and 4 patients were hospitalized for toxicity. Dasatinib inhibited c‐Src both when administered orally and via PFG. Greater mean drug exposure, decreased half‐life, and greater maximum concentration were observed in patients receiving dasatinib via PFG. Eleven baseline CAFs were associated with treatment outcome and 1 CAF, macrophage migration inhibitory factor, was found to be differentially modulated in correlation with SD versus disease progression.

Single‐agent dasatinib failed to demonstrate significant activity in patients with advanced HNSCC, despite c‐Src inhibition. The toxicity profile was consistent with that reported in other solid tumors, and the drug can be given via PFG tube. Cancer 2011. © 2010 American Cancer Society.