A phase II study of single agent OSI-7904L in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN)

e17005 Background: Given the limited efficacy and relative toxicity of chemotherapy for metastatic or recurrent squamous cell carcinoma of the head and neck, further research is needed to both increase the efficacy and decrease the toxicity of treatment. OSI-7904L is a novel liposomal formulation of a non-competitive thymidylate synthase inhibitor. In a phase I study, 12 mg/m2 dosing given every 21 days was both feasible and well tolerated. Methods: This multi-center, two-stage, phase II trial was designed to assess the efficacy and toxicity of OSI-7904L in patients with advanced, refractory SCCHN. A total of 41 patients were to be enrolled by completion of stage II. Enrollment was limited to patients with histologically proven squamous histology, locally recurrent and/or metastatic disease, with no more than one prior chemotherapy regimen. Patients were required to have a performance status of ≤ 2, predicted life expectancy of at least three months and adequate hematopoietic, hepatic and renal function. Efficacy was assessed according to RECIST guidelines, and toxicity was evaluated per CTC AE 3.0. Results: Ten patients enrolled in stage 1. Median age was 60 (range 42–66). Nine were evaluable for response assessment with one withdrawn after one cycle due to a grade 4 papular rash. There were no objective responses while 4 of the 10 patients had stable disease during their first restaging. Median time to progression was 2.5 months for the 9 evaluable patients. Besides the one grade 4 dermatologic reaction, other toxicities were grade 3 fatigue and dehydration, and grade 2 anorexia. Assuming an expected 20% response rate required to initiate enrollment in stage II, the probability of the tenth patient being a responder was less than 3%, thus the study was closed due to lack of response in this population. Conclusions: OSI-7904L was well tolerated similar to the phase I data, but did not demonstrate efficacy in metastatic or recurrent HNSCC patients. Further study of this drug as a single-agent with the current dosing regimen is not recommended. [Table: see text]