The 5-fluorouracil derivative S-1 and pemetrexed (PEM) are antimetabolites that mainly target thymidylate synthase. S-1 received approval for treating non-small cell lung cancer (NSCLC) in Japan in December 2004, and has primarily been administered alone for salvage chemotherapy. To our knowledge, whether PEM resistance influences clinical S-1 activity is unavailable.
Patients with pretreated NSCLC who later underwent S-1 monotherapy were identified from an institutional database. Progression-free survival (PFS) and overall survival (OS) rates after S-1 administration were compared with respect to histological findings using the Kaplan-Meier method and log-rank tests. The PFS and OS rates of patients pretreated with PEM (PEM+) or without (PEM-) for non-squamous NSCLC (n-sq NSCLC) were also compared. The effects of clinical factors on PFS and OS were evaluated using univariate and multivariate analyses with Cox proportional-hazards models.
Among 12 patients (median age, 69 y; range, 39–86 y; female, 33%) who underwent S-1 monotherapy after pretreatment for NSCLC, 65 received PEM-based chemotherapy before S-1 administration. The histological subtypes were adenocarcinoma (65%), squamous cell carcinoma (SCC; 27%) and NSCLC not otherwise specified (8%). Among the patients, 25%, 40%, 25% and 10% had undergone one, two, three and four or more prior chemotherapy regimens, respectively. The median PFS was significantly better for patients with SCC than with n-sq NSCLC (3.4 vs. 2.1 months; HR, 0.62; 95% CI, 0.42–0.90; p = 0.01). Multivariate analysis selected only histology as a statistically significant predictor of a longer PFS. However, median OS did not significantly differ (SCC 8.4 vs. n-sq NSCLC 5.9 months; HR, 0.97; 95% CI, 0.65–1.40; p = 0.86). The PFS were similar between the PEM+ and PEM- groups among the 111 patients with n-sq NSCLC (median 2.1 vs. 2.0 months; HR, 1.17; 95% CI, 0.79–1.74; p = 0.44). The median OS for the PEM+ and PEM- groups were 6.8 and 4.9 months, respectively, not significantly different (HR, 0.70; 95% CI, 0.47–1.06; p = 0.08).
S-1 monotherapy was more effective for SCC than n-sq NSCLC, and prior PEM therapy did not affect S-1 activity in patients with n-sq NSCLC. Further study is warranted.
Clinical trial identification
All authors have declared no conflicts of interest.