Abstract CT303: A multicenter phase ii study of adjuvant chemotherapy with oral fluoropyrimidine s-1 for non-small-cell lung cancer
Authors: Tsuchiya Tomoshi , Yamasaki Naoya , Matsumoto Keitaro , Miyazaki Takuro , Nagayasu Takeshi 
Published: May 2015

Background: S-1, registered as “Teysuno” in European countries, is a novel oral fluoropyrimidine derivative consisting of tegafur (FT) and 2 modulators, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo). FT is a prodrug of 5-fluorouracil (5-FU) and CDHP is a reversible competitive inhibitor of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in the degradation of 5-FU. Although S-1 is used for chemotherapy of gastric cancers, the use of S-1 for the treatment of lung cancer is so far limited. Here, we conducted a feasibility study for using S-1 as a postoperative chemotherapy in 50 patients with curatively resected stage IB-IIIA non-small-cell lung cancer.

Patients and Methods: Adjuvant chemotherapy consisted of 8 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day. Fifty-one patients from 7 institutions were enrolled in this pilot study, from June 2005 to March 2007. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were the incidence and grade of adverse reactions. The Kaplan-Meier method was used to estimate overall survival (OS) and relapse-free survival (RFS). The log-rank test was used to assess the differences between groups.The impacts of 19 clinicopathological factors including EGFR mutation status and immunohistochemical expressions of 5-FU metabolizing enzymes of the resected cancers on survival were analyzed.

Results: Fifty patients were eligible for the study (Pathological stage; IB; n=28, IIA; n=10, IIB; n=5, IIIA; n=7). The completion rate for the planned 8 courses of S-1 administration was 72.0% (36 patients). Total percentage administration amount was 71.1%. Grade 3 adverse reactions such as neutropenia (4.0%), anorexia (4.0%), thrombopenia (2.0%), anemia (2.0%), elevated total bilirubin (2.0%), hypokalemia (2.0%), nausea (2.0%), and diarrhea (2.0%) were observed, but no grade 4 adverse effects were encountered. OS and RFS rates at 5 years were 72.5% and 67.5%, respectively. Among the 19 clinicopathological factors, lymphatic and vessel invasion correlated with the low RFS rate (p&lt;0.05). The OS rate of the patients with squamous cell carcinoma was lower than that of adenocarcinoma (p&lt;0.05). The multivariate analysis indicated high T factors (T2 or more) and immunohistochemically low thymidine synthase expression were correlated with low RFS rates. EGFR mutation status did not affect survival. In cases of recurrence, platinum doublet was mostly selected for further treatment.

Conclusion: Postoperative 1-year administration of S-1 seems feasible as oral adjuvant chemotherapy for lung cancer. The oral formulation and low incidence of adverse reactions permit treatment on an outpatient basis. Survival analysis revealed that this protocol might have significant potential at the adjuvant setting.

Citation Format: Tomoshi Tsuchiya, Naoya Yamasaki, Keitaro Matsumoto, Takuro Miyazaki, Takeshi Nagayasu. A multicenter phase ii study of adjuvant chemotherapy with oral fluoropyrimidine s-1 for non-small-cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT303. doi:10.1158/1538-7445.AM2014-CT303