Introduction
NSCLC, death, tumor, gastrointestinal toxic, gastrointestinal tract, lung cancer, adenocarcinoma
NON-SMALL CELL LUNG CANCER, TUMOR, DISEASE, LUNG CANCER, ADVERSE EFFECTS, ADENOCARCINOMA, NSCLC, ONCOLOGY, DISEASES, GASTRIC CANCER
Surgical resection is considered to be the best curative treatment for early-stage non-small cell lung cancer (NSCLC) [In Japan, postoperative adjuvant chemotherapy with the oral drug tegafur/uracil (UFT) was reported to significantly improve survival in NSCLC patients, especially in adenocarcinoma [On the other hand, the postoperative adjuvant chemotherapy, especially platinum containing regimen, sometimes causes treatment-related death even in good risk patients. Thus, it is not always recommended for elderly patients who often had some complicating diseases and may have potentially impaired health condition. Meanwhile, there is a worldwide-accepted evidence of a population shift toward older ages, which favors an increased risk of developing lung cancer that are more common at a more advanced age [Although NSCLC represents a common health issue in the elderly population, it is difficult to provide evidence-based clinical recommendations for this population, because of the lack of large, well-conducted prospective trials. EORTC and International Society of Geriatric Oncology (SIOG) showed the recommendation for the treatment of NSCLC in an elderly population. They described that postoperative adjuvant chemotherapy is associated with survival benefit in the elderly and therefore should not be denied to patients based on age. Treatment decisions should consider the estimated absolute benefit, life expectancy, treatment tolerance, presence of comorbidities and patient preferences, although less information is available regarding the real benefit and tolerability of the regimens for patients aged > 80 years and the risk versus benefit has not been studied adequately [A review regarding the management of elderly patients with NSCLC suggested the possibility for elderly patients to replace cisplatin to carboplatin for the better tolerability, describing the use of adjuvant chemotherapy in fit elderly patients, although data are insufficient to draw conclusions in patients aged > 75 years [S-1 (Taiho Pharmaceutical Co., Ltd, Tokyo, Japan) is an oral fluoropyrimidine agent consisting of tegafur (a prodrug of 5-fluorouracil [5-FU]), gimeracil (an inhibitor of dihydropyrimidine dehydrogenase, which degrades fluorouracil), and oteracil (an inhibitor of the phosphorylation of fluorouracil in the gastrointestinal tract, resulting in reduction of the gastrointestinal toxic effects of fluorouracil) [As postoperative adjuvant chemotherapy for stage I (tumor diameter greater than 2 cm) disease, the Japan Clinical Oncology Group conducted a randomized phase III study to evaluate S-1 compared with UFT (JCOG0707), with the regimen of 2-week daily administration of S-1 followed by a 1-week rest, in which S-1 was neither superior nor inferior to UFT [To improve the feasibility of S-1, alternate-day administration of S-1 was suggested. In advanced gastric cancer, alternate-day administration (every other day) of S-1 demonstrated the reduction of adverse effects, simultaneously ensured effective blood levels and provided sufficient clinical effects compared with daily administration [Because elderly patients frequently cannot tolerate platinum-doublet chemotherapy, and S-1 monotherapy is shown to be effective to advanced NSCLC in elderly patients, it is reasonable to set S-1 monotherapy as postoperative adjuvant chemotherapy in elderly patients with completely resected NSCLC including pStage II-III.To our knowledge, however, there are no reports of prospective studies using an alternate-day S-1 administration of adjuvant chemotherapy for elderly patients with completely resected NSCLC. Considering these, we designed a multicenter, randomized phase II trial comparing the feasibility and safety of alternate-day administration versus daily administration for 2 weeks followed by a 1-week rest as adjuvant S-1 monotherapy in elderly patients with completely resected stage IA (T1bN0M0)—IIIA NSCLC.