Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase-Low Squamous Cell Lung Cancer

Purpose Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression. Materials and methods In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate. Results Of 32 patients, 8 patients (25%) had an ECOG performance status of 2, and 7 patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0-46.1). Median PFS was 1.3 months (95% CI, 1.3-2.7), and median overall survival was 11.8 months (95% CI, 8.1-not applicable). Conclusion Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.